Skip to main content

Advertisement

Log in

The role of the matricellular protein SPARC in the dynamic interaction between the tumor and the host

  • NON-THEMATIC REVIEW
  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Abstract

Tumor growth is essentially the result of an evolving cross-talk between malignant and surrounding stromal cells (fibroblasts, endothelial cells and inflammatory cells). This heterogeneous mass of extracellular matrix and intermingled cells interact through cell–cell and cell–matrix contacts. Malignant cells also secrete soluble proteins that reach neighbor stromal cells, forcing them to provide the soil on which they will grow and metastasize. Different studies including expression array analysis identified the matricellular protein SPARC as a marker of poor prognosis in different cancer types. Further evidence demonstrated that high SPARC levels are often associated with the most aggressive and highly metastatic tumors. Here we describe the most recent evidence that links SPARC with human cancer progression, the controversy regarding its role in certain human cancers and the physiological processes in which SPARC is involved: epithelial–mesenchymal transition, immune surveillance and angiogenesis. Its relevance as a potential target in cancer therapy is also discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Hanahan, D., & Weinberg, R. A. (2000). The hallmarks of cancer. Cell, 100, 57–70.

    PubMed  CAS  Google Scholar 

  2. Liotta, L. A., & Kohn, E. C. (2001). The microenvironment of the tumour–host interface. Nature, 411, 375–379.

    PubMed  CAS  Google Scholar 

  3. Murphy-Ullrich, J. E. (2001). The de-adhesion activity of matricellular proteins: Is intermediate cell adhesion an adaptive state? Journal of Clinical Investigation, 107(7), 785–790.

    PubMed  CAS  Google Scholar 

  4. Bornstein, P. (2002). Cell–matrix interactions: The view from the outside. Methods in Cell Biology, 69, 7–11.

    PubMed  CAS  Google Scholar 

  5. Sage, E. H. (2001). Regulation of interactions between cells and extracellular matrix: A command performance on several stages. Journal of Clinical Investigation, 107(7), 781–783.

    PubMed  CAS  Google Scholar 

  6. Rosenblatt, S., Bassuk, J. A., Alpers, C. E., Sage, E. H., Timpl, R., & Preissner, K. T. (1997). Differential modulation of cell adhesion by interaction between adhesive and counter-adhesive proteins: Characterization of the binding of vitronectin to osteonectin (BM40, SPARC). Biochemical Journal, 324, 311–319.

    PubMed  CAS  Google Scholar 

  7. Xie, R. L., & Long, G. L. (1995). Role of N-linked glycosylation in human osteonectin. Effect of carbohydrate removal by N-glycanase and site-directed mutagenesis on structure and binding of type V collagen. Journal of Biological Chemistry, 270(39), 23212–23217.

    PubMed  CAS  Google Scholar 

  8. Maurer, P., Hohenadl, C., Hohenester, E., Gohring, W., Timpl, R., & Engel, J. (1995). The C-terminal portion of BM-40 (SPARC/osteonectin) is an autonomously folding and crystallisable domains that binds calcium and collagen IV. Journal of Molecular Biology, 253(2), 347–357.

    PubMed  CAS  Google Scholar 

  9. Raines, E. W., Lane, T. F., Iruela-Arispe, M. L., Ross, R., & Sage, E. H. (1992). The extracellular glycoprotein SPARC interacts with platelet-derived growth factor (PDGF)-AB and BB and inhibits the binding of PDGF to its receptors. Proceedings of the National Academy of Sciences of the United States of America, 89, 1281–1285.

    PubMed  CAS  Google Scholar 

  10. Hasselaar, P., & Sage, E. H. (1992). SPARC antagonizes the effect of basic fibroblast growth factor on the migration of bovine aortic endothelial cells. Journal of Cellular Biochemistry, 49, 272–283.

    PubMed  CAS  Google Scholar 

  11. Tremble, P. M., Lane, T. F., Sage, E. H., & Werb, Z. (1993). SPARC, a secreted protein associated with morphogenesis and tissue remodeling, induces expression of metalloproteinases in fibroblasts through a novel extracellular matrix-dependent pathway. Journal of Cell Biology, 121(6), 1433–1444.

    PubMed  CAS  Google Scholar 

  12. Ledda, M. F., Adris, S., Bravo, A. I., Kairiyama, C., Bover, L., Chernajovsky, Y., et al. (1997). Suppression of SPARC expression by antisense RNA abrogates the tumorigenicity of human melanoma cells. Nature Medicine, 3(2), 171–175.

    PubMed  CAS  Google Scholar 

  13. Lane, T. F., Iruela-Arispe, M. L., & Sage, E. H. (1992). Regulation of gene expression by SPARC during angiogenesis in vitro, changes in fibronectin, thrombospondin-1 and plasminogen activator inhibitor-1. Journal of Biological Chemistry, 267(23), 16736–16745.

    PubMed  CAS  Google Scholar 

  14. Gilles, C., Bassuk, J. A., Pulyaeva, H., Sage, E. H., Foidart, J.-M., & Thompson, E. W. (1998). SPARC/osteonectin induces matrix metalloproteinase 2 activation in human breast cancer cell lines. Cancer Research, 58(23), 5529–5536.

    PubMed  CAS  Google Scholar 

  15. Murphy-Ullrich, J. E., Lane, T. F., Pallero, M. A., & Sage, E. H. (1995). SPARC mediates focal adhesion disassembly in endothelial cells through a follistatin-like region and the Ca2+ binding EF-hand. Journal of Cellular Biochemistry, 57, 341–350.

    PubMed  CAS  Google Scholar 

  16. Brekken, R. A., & Sage, E. H. (2000). SPARC, a matricellular protein: At the crossroads of cell–matrix. Matrix Biology, 19(7), 569–580.

    PubMed  CAS  Google Scholar 

  17. Bradshaw, A. D., Francki, A., Motamed, K., Howe, C., & Sage, E. H. (1999). Primary mesenchymal cells isolated from SPARC-null mice exhibit altered morphology and rates of proliferation. Molecular Biology of the Cell, 10(5), 1569–1579.

    PubMed  CAS  Google Scholar 

  18. Ledda, M. F., Bravo, A. I., Adris, S., Bover, L., Mordoh, J., & Podhajcer, O. L. (1997). The expression on the secreted protein acidic and rich in cysteine (SPARC) is associated with the neoplastic progression of human melanoma. Journal of Investigative Dermatology, 108(2), 210–214.

    PubMed  CAS  Google Scholar 

  19. Rumpler, G., Becker, B., Hafner, C., McClelland, M., Stolz, W., Landthaler, M., et al. (2003). Identification of differentially expressed genes in models of melanoma progression by cDNA array analysis: SPARC, MIF and a novel cathepsin protease characterize aggressive phenotypes. Experimental Dermatology, 12(6), 761–771.

    PubMed  CAS  Google Scholar 

  20. Massi, D., Franchi, A., Borgognoni, L., Reali, U. M., & Santucci, M. (1999). Osteonectin expression correlates with clinical outcome in thin cutaneous malignant melanomas. Human Pathology, 30(3), 339–344.

    PubMed  CAS  Google Scholar 

  21. Ikuta, Y., Nakatsura, T., Kageshita, T., Fukushima, S., Ito, S., Wakamatsu, K., et al. (2005). Highly sensitive detection of melanoma at an early stage based on the increased serum secreted protein acidic and rich in cysteine and glypican-3 levels. Clinical Cancer Research, 11(22), 8079–8088.

    PubMed  CAS  Google Scholar 

  22. Sosa, M. S., Girotti, M. R., Salvatierra, E., Prada, F., de Olmo, J. A., Gallango, S. J., et al. (2007). Proteomic analysis identified N-cadherin, clusterin, and HSP27 as mediators of SPARC (secreted protein, acidic and rich in cysteines) activity in melanoma cells. Proteomics, 7(22), 4123–4134.

    PubMed  CAS  Google Scholar 

  23. Smit, D. J., Gardiner, B. B., & Sturm, R. A. (2007). Osteonectin downregulates E-cadherin, induces osteopontin and focal adhesion kinase activity stimulating an invasive melanoma phenotype. International Journal of Cancer, 121(12), 2653–2660.

    CAS  Google Scholar 

  24. Porter, P. L., Sage, E. H., Lane, T. F., Funk, S. E., & Gown, A. M. (1995). Distribution of SPARC in normal and neoplastic human tissue. Journal of Histochemistry and Cytochemistry, 43(8), 791–800.

    PubMed  CAS  Google Scholar 

  25. Bellahcene, A., & Castronovo, V. (1995). Increased expression of osteonectin and osteopontin, two bone matrix proteins, in human breast cancer. American Journal of Pathology, 146(1), 95–100.

    PubMed  CAS  Google Scholar 

  26. Podhajcer, O. L., Wolf, C., Lefebvre, O., Segain, J. P., Rouyer, N., Stoll, I., et al. (1996). Comparative expression of the SPARC and stromelysin-3 genes in mammary tumors. The Breast, 5, 13–20.

    Google Scholar 

  27. Jones, C., Mackay, A., Grigoriadis, A., Cossu, A., Reis-Filho, J. S., Fulford, L., et al. (2004). Expression profiling of purified normal human luminal and myoepithelial breast cells: Identification of novel prognostic markers for breast cancer. Cancer Research, 64(9), 3037–3045.

    PubMed  CAS  Google Scholar 

  28. Lien, H. C., Hsiao, Y. H., Lin, Y. S., Yao, Y. T., Juan, H. F., Kuo, W. H., et al. (2007). Molecular signatures of metaplastic carcinoma of the breast by large-scale transcriptional profiling: Identification of genes potentially related to epithelial–mesenchymal transition. Oncogene, 26(57), 7859–7871.

    PubMed  CAS  Google Scholar 

  29. Barth, P. J., Moll, R., & Ramaswamy, A. (2005). Stromal remodeling and SPARC (secreted protein acid rich in cysteine) expression in invasive ductal carcinomas of the breast. Virchows Archiv, 446(5), 532–536.

    PubMed  CAS  Google Scholar 

  30. Parker, B. S., Argani, P., Cook, B. P., Liangfeng, H., Chartrand, S. D., Zhang, M., et al. (2004). Alterations in vascular gene expression in invasive breast carcinoma. Cancer Research, 64(21), 7857–7866.

    PubMed  CAS  Google Scholar 

  31. Iacobuzio-Donahue, C. A., Argani, P., Hempen, P. M., Jones, J., & Kern, S. E. (2002). The desmoplastic response to infiltrating breast carcinoma: Gene expression at the site of primary invasion and implications for comparisons between tumor types. Cancer Research, 62(18), 5351–5357.

    PubMed  CAS  Google Scholar 

  32. Graham, J. D., Balleine, R. L., Milliken, J. S., Bilous, A. M., & Clarke, C. L. (1997). Expression of osteonectin mRNA in human breast tumours is inversely correlated with oestrogen receptor content. European Journal of Cancer, 33(10), 1654–1660.

    PubMed  CAS  Google Scholar 

  33. Lakhani, S. R., Reis-Filho, J. S., Fulford, L., Penault-Llorca, F., van der Vijver, M., Parry, S., et al. (2005). Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype. Clinical Cancer Research, 11(14), 5175–5180.

    PubMed  CAS  Google Scholar 

  34. Watkins, G., Douglas-Jones, A., Bryce, R., Mansel, R. E., & Jiang, W. G. (2005). Increased levels of SPARC (osteonectin) in human breast cancer tissues and its association with clinical outcomes. Prostaglandins, Leukotrienes and Essential Fatty Acids, 72(4), 267–272.

    CAS  Google Scholar 

  35. Rempel, S. A., Golembieski, W. A., Ge, S., Lemke, N., Elisevich, K., Mikkelsen, T., et al. (1998). SPARC: A signal of astrocytic neoplastic transformation and reactive response in human primary and xenograft gliomas. Journal of Neuropathology and Experimental Neurology, 57(12), 1112–1121.

    PubMed  CAS  Google Scholar 

  36. Golembieski, W. A., Ge, S., Nelson, K., Mikkelsen, T., & Rempel, S. A. (1999). Increased SPARC expression promotes U87 glioblastoma invasion in vitro. International Journal of Developmental Neuroscience, 17(5–6), 463–472.

    PubMed  CAS  Google Scholar 

  37. Rich, J. N., Shi, Q., Hjelmeland, M., Cummings, T. J., Kuan, C. T., Bigner, D. D., et al. (2003). Bone-related genes expressed in advanced malignancies induce invasion and metastasis in a genetically defined human cancer model. Journal of Biological Chemistry, 278(18), 15951–15957.

    PubMed  CAS  Google Scholar 

  38. Schultz, C., Lemke, N., Ge, S., Golembieski, W. A., & Rempel, S. A. (2002). Secreted protein acidic and rich in cysteine promotes glioma invasion and delays tumor growth in vivo. Cancer Research, 62, 6270–6277.

    PubMed  CAS  Google Scholar 

  39. Vajkoczy, P., Manger, M. D., Goldbrunner, R., Ge, S., Fong, T. A., Vollmar, B., et al. (2000). Targeting angiogenesis inhibits tumor infiltration and expression of the pro-invasive protein SPARC. International Journal of Cancer, 87(2), 261–268.

    CAS  Google Scholar 

  40. Shi, Q., Bao, S., Maxwell, J. A., Reese, E. D., Friedman, H. S., Bigner, D. D., et al. (2004). Secreted protein acidic, rich in cysteine (SPARC), mediates cellular survival of gliomas through AKT activation. Journal of Biological Chemistry, 279(50), 52200–52209.

    PubMed  CAS  Google Scholar 

  41. McClung, H. M., Thomas, S. L., Osenkowski, P., Toth, M., Menon, P., Raz, A., et al. (2007). SPARC upregulates MT1-MMP expression, MMP-2 activation, and the secretion and cleavage of galectin-3 in U87MG glioma cells. Neuroscience Letters, 419(2), 172–177.

    PubMed  CAS  Google Scholar 

  42. Minn, A. J., Gupta, G. P., Siegel, P. M., Bos, P. D., Shu, W., Giri, D. D., et al. (2005). Genes that mediate breast cancer metastasis to lung. Nature, 436(7050), 518–524.

    PubMed  CAS  Google Scholar 

  43. Campo-McKnight, D. A., Sosnoski, D. M., Koblinski, J. E., & Gay, C. V. (2006). Roles of osteonectin in the migration of breast cancer cells into bone. Journal of Cellular Biochemistry, 97(2), 288–302.

    PubMed  Google Scholar 

  44. Jacob, K., Webber, M., Benayahu, D., & Kleinman, H. K. (1999). Osteonectin promotes prostate cancer cell migration and invasion: Possible mechanism for metastasis to bone. Cancer Research, 59(17), 4453–4457.

    PubMed  CAS  Google Scholar 

  45. De, S., Chen, J., Narizhneva, N. V., Heston, W., Brainard, J., Sage, E. H., et al. (2003). molecular pathway for cancer metastasis to bone. Journal of Biological Chemistry, 278(40), 39044–39050.

    PubMed  CAS  Google Scholar 

  46. Chen, N., Ye, X. C., Chu, K., Navone, N. M., Sage, E. H., Yu-Lee, L. Y., et al. (2007). A secreted isoform of ErbB3 promotes osteonectin expression in bone and enhances the invasiveness of prostate cancer cells. Cancer Research, 67(14), 6544–6548.

    PubMed  CAS  Google Scholar 

  47. Koblinski, J. E., Kaplan-Singer, B. R., VanOsdol, S. J., Wu, M., Engbring, J. A., Wang, S., et al. (2005). Endogenous osteonectin/SPARC/BM-40 expression inhibits MDA-MB-231 breast cancer cell metastasis. Cancer Research, 65(16), 7370–7377.

    PubMed  CAS  Google Scholar 

  48. Finocchiaro, G., Mancuso, F. M., Cittaro, D., & Muller, H. (2007). Graph-based identification of cancer signaling pathways from published gene expression signatures using PubLiME. Nucleic Acids Research, 35(7), 2343–2355.

    PubMed  CAS  Google Scholar 

  49. Chlenski, A., Liu, S., Crawford, S. E., Volpert, O. V., DeVries, G. H., Evangelista, A., et al. (2002). SPARC is a key Schwannian-derived inhibitor controlling neuroblastoma tumor angiogenesis. Cancer Research, 62(24), 7357–7363.

    PubMed  CAS  Google Scholar 

  50. Chlenski, A., Liu, S., Baker, L. J., Yang, Q., Tian, Y., Salwen, H. R., et al. (2004). Neuroblastoma angiogenesis is inhibited with a folded synthetic molecule corresponding to the epidermal growth factor-like module of the follistatin domain of SPARC. Cancer Research, 64(20), 7420–7425.

    PubMed  CAS  Google Scholar 

  51. Said, N., Socha, M. J., Olearczyk, J. J., Elmarakby, A. A., Imig, J. D., & Motamed, K. (2007). Normalization of the ovarian cancer microenvironment by SPARC. Molecular Cancer Research, 5(10), 1015–1030.

    PubMed  CAS  Google Scholar 

  52. Said, N. A., Najwer, I., Socha, M. J., Fulton, D. J., Mok, S. C., & Motamed, K. (2007). SPARC inhibits LPA-mediated mesothelial–ovarian cancer cell crosstalk. Neoplasia, 9(1), 23–35.

    PubMed  CAS  Google Scholar 

  53. Yiu, G. K., Chan, W. Y., Ng, S. W., Chan, P. S., Cheung, K. K., Berkowitz, R. S., et al. (2001). SPARC (secreted protein acidic and rich in cysteine) induces apoptosis in ovarian cancer cells. American Journal of Pathology, 159(2), 609–622.

    PubMed  CAS  Google Scholar 

  54. Mok, S. C., Chan, W. Y., Wong, K. K., Muto, M. G., & Berkowitz, R. S. (1996). SPARC, an extracellular matrix protein with tumor-suppressing activity in human ovarian epithelial cells. Oncogene, 12, 1895–1901.

    PubMed  CAS  Google Scholar 

  55. Said, N., & Motamed, K. (2005). Absence of host-secreted protein acidic and rich in cysteine (SPARC) augments peritoneal ovarian carcinomatosis. American Journal of Pathology, 167(6), 1739–1752.

    PubMed  CAS  Google Scholar 

  56. Brown, T. J., Shaw, P. A., Karp, X., Huynh, M. H., Begley, H., & Ringuette, M. J. (1999). Activation of SPARC expression in reactive stroma associated with human epithelial ovarian cancer. Gynecologic Oncology, 75(1), 25–33.

    PubMed  CAS  Google Scholar 

  57. Tai, I. T., Dai, M., Owen, D. A., & Chen, L. B. (2005). Genome-wide expression analysis of therapy-resistant tumors reveals SPARC as a novel target for cancer therapy. Journal of Clinical Investigation, 115(6), 1492–1502.

    PubMed  CAS  Google Scholar 

  58. Taghizadeh, F., Tang, M. J., & Tai, I. T. (2007). Synergism between vitamin D and secreted protein acidic and rich in cysteine-induced apoptosis and growth inhibition results in increased susceptibility of therapy-resistant colorectal cancer cells to chemotherapy. Molecular Cancer Therapeutics, 6(1), 309–317.

    PubMed  CAS  Google Scholar 

  59. Tang, M. J., & Tai, I. T. (2007). A novel interaction between procaspase 8 and SPARC enhances apoptosis and potentiates chemotherapy sensitivity in colorectal cancers. Journal of Biological Chemistry, 282(47), 34457–34467.

    PubMed  CAS  Google Scholar 

  60. Yang, E., Kang, H. J., Koh, K. H., Rhee, H., Kim, N. K., & Kim, H. (2007). Frequent inactivation of SPARC by promoter hypermethylation in colon cancers. International Journal of Cancer, 121(3), 567–575.

    CAS  Google Scholar 

  61. Wiese, A. H., Auer, J., Lassmann, S., Nahrig, J., Rosenberg, R., Hofler, H., et al. (2007). Identification of gene signatures for invasive colorectal tumor cells. Cancer Detection and Prevention, 31(4), 282–295.

    PubMed  CAS  Google Scholar 

  62. Nguyen, Q. D., De Wever, O., Bruyneel, E., Hendrix, A., Xie, W. Z., Lombet, A., et al. (2005). Commutators of PAR-1 signaling in cancer cell invasion reveal an essential role of the Rho–Rho kinase axis and tumor microenvironment. Oncogene, 24(56), 8240–8251.

    PubMed  CAS  Google Scholar 

  63. Porte, H., Chastre, E., Prevot, S., Nordlinger, B., Empereur, S., Basset, P., et al. (1995). Neoplastic progression of human colorectal cancer is associated with overexpression of the stromelysin-3 and BM-40/SPARC genes. International Journal of Cancer, 64, 70–75.

    CAS  Google Scholar 

  64. Guweidhi, A., Kleeff, J., Adwan, H., Giese, N. A., Wente, M. N., Giese, T., et al. (2005). Osteonectin influences growth and invasion of pancreatic cancer cells. Annals of Surgery, 242(2), 224–234.

    PubMed  Google Scholar 

  65. Infante, J. R., Matsubayashi, H., Sato, N., Tonascia, J., Klein, A. P., Riall, T. A., et al. (2007). Peritumoral fibroblast SPARC expression and patient outcome with resectable pancreatic adenocarcinoma. Journal of Clinical Oncology, 25(3), 319–325.

    PubMed  Google Scholar 

  66. Koukourakis, M. I., Giatromanolaki, A., Brekken, R. A., Sivridis, E., Gatter, K. C., Harris, A. L., et al. (2003). Enhanced expression of SPARC/osteonectin in the tumor-associated stroma of non-small cell lung cancer is correlated with markers of hypoxia/acidity and with poor prognosis of patients. Cancer Research, 63(17), 5376–5380.

    PubMed  CAS  Google Scholar 

  67. Sato, N., Fukushima, N., Maehara, N., Matsubayashi, H., Koopmann, J., Su, G. H., et al. (2003). SPARC/osteonectin is a frequent target for aberrant methylation in pancreatic adenocarcinoma and a mediator of tumor–stromal interactions. Oncogene, 22(32), 5021–5030.

    PubMed  CAS  Google Scholar 

  68. López-Haber, C., Gottifredi, V., Llera, A. S., Salvatierra, E., Prada, F., Alonso, L., et al. (2008). SPARC modulates the proliferation of stromal but not melanoma cells unless endogenous SPARC expression is downregulated. International Journal of Cancer, 122(7), 1465–1475.

    Google Scholar 

  69. Prada, F., Benedetti, L. G., Bravo, A. I., Alvarez, M. J., Carbone, C., & Podhajcer, O. L. (2007). SPARC endogenous level, rather than fibroblast-produced SPARC or stroma reorganization induced by SPARC, is responsible for melanoma cell growth. Journal of Investigative Dermatology, 127(11), 2618–2628.

    PubMed  CAS  Google Scholar 

  70. Brekken, R. A., Puolakkainen, P., Graves, D. C., Workman, G., Lubkin, S. R., & Sage, E. H. (2003). Enhanced growth of tumors in SPARC null mice is associated with changes in the ECM. Journal of Clinical Investigation, 111(4), 487–495.

    PubMed  CAS  Google Scholar 

  71. Sangaletti, S., Stoppacciaro, A., Guiducci, C., Torrisi, M. R., & Colombo, M. P. (2003). Leukocyte, rather than tumor-produced SPARC, determines stroma and collagen type IV deposition in mammary carcinoma. Journal of Experimental Medicine, 198(10), 1475–1485.

    PubMed  CAS  Google Scholar 

  72. Framson, P. E., & Sage, E. H. (2004). SPARC and tumor growth: Where the seed meets the soil? Journal of Cellular Biochemistry, 92(4), 679–690.

    PubMed  CAS  Google Scholar 

  73. Gooden, M. D., Vernon, R. B., Bassuk, J. A., & Sage, E. H. (1999). Cell cycle-dependent nuclear location of the matricellular protein SPARC: Association with the nuclear matrix. Journal of Cellular Biochemistry, 74(2), 152–167.

    PubMed  CAS  Google Scholar 

  74. Sodek, J., Zhu, B., Huynh, M. H., Brown, T. J., & Ringuette, M. (2002). Novel functions of the matricellular proteins osteopontin and osteonectin/SPARC. Connective Tissue Research, 43(2–3), 308–319.

    PubMed  CAS  Google Scholar 

  75. Yan, Q., Weaver, M., Perdue, N., & Sage, E. H. (2005). Matricellular protein SPARC is translocated to the nuclei of immortalized murine lens epithelial cells. Journal of Cellular Physiology, 203(1), 286–294.

    PubMed  CAS  Google Scholar 

  76. Sage, E. H., Johnson, C., & Bornstein, P. (1984). Characterization of a novel serum albumin-binding glycoprotein secreted by endothelial cells in culture. Journal of Biological Chemistry, 259, 3993–4007.

    PubMed  CAS  Google Scholar 

  77. Funk, S. E., & Sage, E. H. (1993). Differential effects of SPARC and cationic SPARC peptides on DNA synthesis by endothelial cells and fibroblasts. Journal of Cellular Physiology, 154, 53–63.

    PubMed  CAS  Google Scholar 

  78. Funk, S. E., & Sage, E. H. (1991). The Ca2+-binding glycoprotein SPARC modulates cell cycle progression in bovine aortic endothelial cells. Proceedings of the National Academy of Sciences of the United States of America, 88, 2648–2652.

    PubMed  CAS  Google Scholar 

  79. Kupprion, C., Motamed, K., & Sage, E. H. (1998). SPARC (BM-40, Osteonectin) inhibits the mitogenic effect of vascular endothelial growth factor on microvascular endothelial cells. Journal of Biological Chemistry, 273(45), 29635–29640.

    PubMed  CAS  Google Scholar 

  80. Lau, C. P., Poon, R. T., Cheung, S. T., Yu, W. C., & Fan, S. T. (2006). SPARC and Hevin expression correlate with tumour angiogenesis in hepatocellular carcinoma. Journal of Pathology, 210(4), 459–468.

    PubMed  CAS  Google Scholar 

  81. Charest, A., Pepin, A., Shetty, R., Cote, C., Voisine, P., Dagenais, F., et al. (2006). Distribution of SPARC during neovascularisation of degenerative aortic stenosis. Heart, 92(12), 1844–1849.

    PubMed  CAS  Google Scholar 

  82. Iruela Arispe, M. L., Lane, T. F., Redmond, D., Reilly, M., Bolender, R. P., Kavanagh, T. J., et al. (1995). Expression of SPARC during development of the chicken chorioallantoic membrane: Evidence for regulated proteolysis in vivo. Molecular Biology of the Cell, 6(3), 327–343.

    PubMed  CAS  Google Scholar 

  83. Lane, T. F., Iruela-Arispe, M. L., Johnson, R. S., & Sage, E. H. (1994). SPARC is a source of copper-binding peptides that stimulate angiogenesis. Journal of Cell Biology, 125, 929–943.

    PubMed  CAS  Google Scholar 

  84. Sage, E. H., Reed, M., Funk, S. E., Truong, T., Steadele, M., Puolakkainen, P., et al. (2003). Cleavage of the matricellular protein SPARC by matrix metalloproteinase 3 produces polypeptides that influence angiogenesis. Journal of Biological Chemistry, 278(39), 37849–37857.

    PubMed  CAS  Google Scholar 

  85. Sasaki, T., Miosge, N., & Timpl, R. (1999). Immunochemical and tissue analysis of protease generated neoepitopes of BM-40 (osteonectin, SPARC) which are correlated to a higher affinity binding to collagens. Matrix Biology, 18(5), 499–508.

    PubMed  CAS  Google Scholar 

  86. Kato, Y., Lewalle, J. M., Baba, Y., Tsukuda, M., Sakai, N., Baba, M., et al. (2001). Induction of SPARC by VEGF in human vascular endothelial cells. Biochemical and Biophysical Research Communications, 287(2), 422–426.

    PubMed  CAS  Google Scholar 

  87. Nozaki, M., Sakurai, E., Raisler, B. J., Baffi, J. Z., Witta, J., Ogura, Y., et al. (2006). Loss of SPARC-mediated VEGFR-1 suppression after injury reveals a novel antiangiogenic activity of VEGF-A. Journal of Clinical Investigation, 116(2), 422–429.

    PubMed  CAS  Google Scholar 

  88. Ferrari, G., Pintucci, G., Seghezzi, G., Hyman, K., Galloway, A. C., & Mignatti, P. (2006). VEGF, a prosurvival factor, acts in concert with TGF-beta1 to induce endothelial cell apoptosis. Proceedings of the National Academy of Sciences of the United States of America, 103(46), 17260–17265.

    PubMed  CAS  Google Scholar 

  89. Choi, M. E., & Ballermann, B. J. (1995). Inhibition of capillary morphogenesis and associated apoptosis by dominant negative mutant transforming growth factor-beta receptors. Journal of Biological Chemistry, 270(36), 21144–21150.

    PubMed  CAS  Google Scholar 

  90. Thiery, J. P. (2002). Epithelial–mesenchymal transitions in tumour progression. Nature Reviews. Cancer, 2(6), 442–454.

    PubMed  CAS  Google Scholar 

  91. Cano, A., Perez-Moreno, M. A., Rodrigo, I., Locascio, A., Blanco, M. J., del Barrio, M. G., et al. (2000). The transcription factor snail controls epithelial–mesenchymal transitions by repressing E-cadherin expression. Nature Cell Biology, 2(2), 76–83.

    PubMed  CAS  Google Scholar 

  92. De Craene, B., van Roy, F., & Berx, G. (2005). Unraveling signalling cascades for the Snail family of transcription factors. Cellular Signalling, 17(5), 535–547.

    PubMed  Google Scholar 

  93. Moreno-Bueno, G., Cubillo, E., Sarrio, D., Peinado, H., Rodriguez-Pinilla, S. M., Villa, S., et al. (2006). Genetic profiling of epithelial cells expressing E-cadherin repressors reveals a distinct role for Snail, Slug, and E47 factors in epithelial–mesenchymal transition. Cancer Research, 66(19), 9543–9556.

    PubMed  CAS  Google Scholar 

  94. Robert, G., Gaggioli, C., Bailet, O., Chavey, C., Abbe, P., Aberdam, E., et al. (2006). SPARC represses E-cadherin and induces mesenchymal transition during melanoma development. Cancer Research, 66(15), 7516–7523.

    PubMed  CAS  Google Scholar 

  95. Alonso, S. R., Tracey, L., Ortiz, P., Perez-Gomez, B., Palacios, J., Pollan, M., et al. (2007). A high-throughput study in melanoma identifies epithelial–mesenchymal transition as a major determinant of metastasis. Cancer Research, 67(7), 3450–3460.

    PubMed  CAS  Google Scholar 

  96. Bierie, B., & Moses, H. L. (2006). Tumour microenvironment: TGFbeta: The molecular Jekyll and Hyde of cancer. Nature Reviews. Cancer, 6(7), 506–520.

    PubMed  CAS  Google Scholar 

  97. Ford, R., Wang, G., Jannati, P., Adler, D., Racanelli, P., Higgins, P. J., et al. (1993). Modulation of SPARC expression during butyrate-induced terminal differentiation of cultured human keratinocytes: Regulation via a TGF-beta-dependent pathway. Experimental Cell Research, 206(2), 261–275.

    PubMed  CAS  Google Scholar 

  98. Bassuk, J. A., Pichler, R., Rothmier, J. D., Pippen, J., Gordon, K., Meek, R. L., et al. (2000). Induction of TGF-beta1 by the matricellular protein SPARC in a rat model of glomerulonephritis. Kidney International, 57(1), 117–128.

    PubMed  CAS  Google Scholar 

  99. Francki, A., Bradshaw, A. D., Bassuk, J. A., Howe, C. C., Couser, W. G., & Sage, E. H. (1999). SPARC regulates the expression of collagen type I and transforming growth factor-beta1 in mesangial cells. Journal of Biological Chemistry, 274(45), 32145–32152.

    PubMed  CAS  Google Scholar 

  100. Reed, M. J., Vernon, R. B., Abrass, I. B., & Sage, E. H. (1994). TGF-b 1 induces the expression of type I collagen and SPARC, and enhances contraction of collagen gels, by fibroblasts from young and aged donors. Journal of Cellular Physiology, 158(1), 169–179.

    PubMed  CAS  Google Scholar 

  101. Shiba, H., Uchida, Y., Kamihagi, K., Sakata, M., Fujita, T., Nakamura, S., et al. (2001). Transforming growth factor-beta1 and basic fibroblast growth factor modulate osteocalcin and osteonectin/SPARC syntheses in vitamin-D-activated pulp cells. Journal of Dental Research, 80(7), 1653–1659.

    Article  PubMed  CAS  Google Scholar 

  102. Wrana, J. L., Overall, C. M., & Sodek, J. (1991). Regulation of the expression of a secreted acidic protein rich in cysteine (SPARC) in human fibroblasts by transforming growth factor beta. Comparison of transcriptional and post-transcriptional control with fibronectin and type I collagen. European Journal of Biochemistry, 197, 519–528.

    PubMed  CAS  Google Scholar 

  103. Pavasant, P., Yongchaitrakul, T., Pattamapun, K., & Arksornnukit, M. (2003). The synergistic effect of TGF-beta and 1,25-dihydroxyvitamin D3 on SPARC synthesis and alkaline phosphatase activity in human pulp fibroblasts. Archives of Oral Biology, 48(10), 717–722.

    PubMed  CAS  Google Scholar 

  104. Francki, A., McClure, T. D., Brekken, R. A., Motamed, K., Murri, C., Wang, T., et al. (2004). SPARC regulates TGF-beta1-dependent signaling in primary glomerular mesangial cells. Journal of Cellular Biochemistry, 91(5), 915–925.

    PubMed  CAS  Google Scholar 

  105. Schiemann, B. J., Neil, J. R., & Schiemann, W. P. (2003). SPARC inhibits epithelial cell proliferation in part through stimulation of the TGF-beta-signaling system. Molecular Biology of the Cell, 14(10), 3977–3988.

    PubMed  CAS  Google Scholar 

  106. Bradshaw, A. D., Reed, M. J., Carbon, J. G., Pinney, E., Brekken, R. A., & Sage, E. H. (2001). Increased fibrovascular invasion of subcutaneous polyvinyl alcohol sponges in SPARC-null mice. Wound Repair and Regeneration, 9(6), 522–530.

    PubMed  CAS  Google Scholar 

  107. Peinado, H., Quintanilla, M., & Cano, A. (2003). Transforming growth factor beta-1 induces snail transcription factor in epithelial cell lines: Mechanisms for epithelial mesenchymal transitions. Journal of Biological Chemistry, 278(23), 21113–21123.

    PubMed  CAS  Google Scholar 

  108. McLean, G. W., Carragher, N. O., Avizienyte, E., Evans, J., Brunton, V. G., & Frame, M. C. (2005). The role of focal-adhesion kinase in cancer—A new therapeutic opportunity. Nature Reviews. Cancer, 5(7), 505–515.

    PubMed  CAS  Google Scholar 

  109. Shi, Q., Bao, S., Song, L., Wu, Q., Bigner, D. D., Hjelmeland, A. B., et al. (2007). Targeting SPARC expression decreases glioma cellular survival and invasion associated with reduced activities of FAK and ILK kinases. Oncogene, 26(28), 4084–4094.

    PubMed  CAS  Google Scholar 

  110. Coussens, L. M., & Werb, Z. (1996). Matrix metalloproteinases and the development of cancer. Chemistry & Biology, 3, 895–904.

    CAS  Google Scholar 

  111. Alvarez, M. J., Prada, F., Salvatierra, E., Bravo, A. I., Lutzky, V. P., Carbone, C., et al. (2005). Secreted protein acidic and rich in cysteine produced by human melanoma cells modulates polymorphonuclear leukocyte recruitment and antitumor cytotoxic capacity. Cancer Research, 65(12), 5123–5132.

    PubMed  CAS  Google Scholar 

  112. Savani, R. C., Zhou, Z., Arguiri, E., Wang, S., Vu, D., Howe, C. C., et al. (2000). Bleomycin-induced pulmonary injury in mice deficient in SPARC. AJP—Lung Cellular and Molecular Physiology, 279(4), L743–L750.

    PubMed  CAS  Google Scholar 

  113. Sangaletti, S., Gioiosa, L., Guiducci, C., Rotta, G., Rescigno, M., Stoppacciaro, A., et al. (2005). Accelerated dendritic-cell migration and T-cell priming in SPARC-deficient mice. Journal of Cell Science, 118(Pt 16), 3685–3694.

    PubMed  CAS  Google Scholar 

  114. Rempel, S. A., Hawley, R. C., Gutierrez, J. A., Mouzon, E., Bobbitt, K. R., Lemke, N., et al. (2007). Splenic and immune alterations of the Sparc-null mouse accompany a lack of immune response. Genes and Immunity, 8(3), 262–274.

    PubMed  CAS  Google Scholar 

  115. Vannahme, C., Gosling, S., Paulsson, M., Maurer, P., & Hartmann, U. (2003). Characterization of SMOC-2, a modular extracellular calcium-binding protein. Biochemical Journal, 373(Pt 3), 805–814.

    PubMed  CAS  Google Scholar 

  116. Rocnik, E. F., Liu, P., Sato, K., Walsh, K., & Vaziri, C. (2006). The novel SPARC family member SMOC-2 potentiates angiogenic growth factor activity. Journal of Biological Chemistry, 281(32), 22855–22864.

    PubMed  CAS  Google Scholar 

  117. Girard, J.-P., & Springer, T. A. (1995). Cloning from purified high endothelial venule cells of hevin, a close relative of the antiadhesive extracellular matrix protein SPARC. Immunity, 2, 113–123.

    PubMed  CAS  Google Scholar 

  118. Girard, J.-P., & Springer, T. A. (1996). Modulation of endothelial cell adhesion by hevin, an acidic protein associated with high endothelial venules. Journal of Biological Chemistry, 271(8), 4511–4517.

    PubMed  CAS  Google Scholar 

  119. Nelson, P. S., Plymate, S. R., Wang, K., True, L. D., Ware, J. L., Gan, L., et al. (1998). Hevin, an antiadhesive extracellular matrix protein, is down-regulated in metastatic prostate adenocarcinoma. Cancer Research, 58(2), 232–236.

    PubMed  CAS  Google Scholar 

  120. Bendik, I., Schraml, P., & Ludwig, C. U. (1998). Characterization of MAST9/Hevin, a SPARC-like protein, that is down-regulated in non-small cell lung cancer. Cancer Research, 58(4), 626–629.

    PubMed  CAS  Google Scholar 

  121. Claeskens, A., Ongenae, N., Neefs, J. M., Cheyns, P., Kaijen, P., Cools, M., et al. (2000). Hevin is down-regulated in many cancers and is a negative regulator of cell growth and proliferation. British Journal of Cancer, 82(6), 1123–1130.

    PubMed  CAS  Google Scholar 

  122. Esposito, I., Kayed, H., Keleg, S., Giese, T., Sage, E. H., Schirmacher, P., et al. (2007). Tumor-suppressor function of SPARC-like protein 1/Hevin in pancreatic cancer. Neoplasia, 9(1), 8–17.

    PubMed  CAS  Google Scholar 

  123. Jazaeri, A. A., Awtrey, C. S., Chandramouli, G. V., Chuang, Y. E., Khan, J., Sotiriou, C., et al. (2005). Gene expression profiles associated with response to chemotherapy in epithelial ovarian cancers. Clinical Cancer Research, 11(17), 6300–6310.

    PubMed  CAS  Google Scholar 

  124. Briggs, J., Chamboredon, S., Castellazzi, M., Kerry, J. A., & Bos, T. J. (2002). Transcriptional upregulation of SPARC, in response to c-Jun overexpression, contributes to increased motility and invasion of MCF7 breast cancer cells. Oncogene, 21(46), 7077–7091.

    PubMed  CAS  Google Scholar 

  125. Lopez, M. V., Blanco, P., Viale, D. L., Cafferata, E. G., Carbone, C., Gould, D., et al. (2006). Expression of a suicidal gene under control of the human secreted protein acidic and rich in cysteine (SPARC) promoter in tumor or stromal cells led to the inhibition of tumor cell growth. Molecular Cancer Therapeutics, 5(10), 2503–2511.

    PubMed  CAS  Google Scholar 

  126. Zajchowski, D. A., Bartholdi, M. F., Gong, Y., Webster, L., Liu, H.-L., Munishkin, A., et al. (2001). Identification of gene expression profiles that predict the aggressive behavior of breast cancer cells. Cancer Research, 61(13), 5168–5178.

    PubMed  CAS  Google Scholar 

  127. Woelfle, U., Cloos, J., Sauter, G., Riethdorf, L., Janicke, F., van Diest, P., et al. (2003). Molecular signature associated with bone marrow micrometastasis in human breast cancer. Cancer Research, 63(18), 5679–5684.

    PubMed  CAS  Google Scholar 

  128. Watkins, G., Martin, T. A., Bryce, R., Mansel, R. E., & Jiang, W. G. (2005). Gamma-Linolenic acid regulates the expression and secretion of SPARC in human cancer cells. Prostaglandins, Leukotrienes and Essential Fatty Acids, 72(4), 273–278.

    CAS  Google Scholar 

  129. Castronovo, V., & Bellahcene, A. (1998). Evidence that breast cancer associated microcalcifications are mineralized malignant cells. International Journal of Oncology, 12(2), 305–308.

    PubMed  CAS  Google Scholar 

  130. Porter, D., Lahti-Domenici, J., Keshaviah, A., Bae, Y. K., Argani, P., Marks, J., et al. (2003). Molecular markers in ductal carcinoma in situ of the breast. Molecular Cancer Research, 1(5), 362–375.

    PubMed  CAS  Google Scholar 

  131. Dairkee, S. H., Ji, Y., Ben, Y., Moore, D. H., Meng, Z., & Jeffrey, S. S. (2004). A molecular ‘signature’ of primary breast cancer cultures; patterns resembling tumor tissue. BMC Genomics, 5, 47.

    PubMed  Google Scholar 

  132. Amatschek, S., Koenig, U., Auer, H., Steinlein, P., Pacher, M., Gruenfelder, A., et al. (2004). Tissue-wide expression profiling using cDNA subtraction and microarrays to identify tumor-specific genes. Cancer Research, 64(3), 844–856.

    PubMed  CAS  Google Scholar 

  133. Jansen, M. P. H. M., Foekens, J. A., van Staveren, I. L., Dirkzwager-Kiel, M. M., Ritstier, K., Look, M. P., et al. (2005). Molecular classification of tamoxifen-resistant breast carcinomas by gene expression profiling. Journal of Clinical Oncology, 23(4), 732–740.

    PubMed  CAS  Google Scholar 

  134. Sturm, R. A., Satyamoorthy, K., Meier, F., Gardiner, B. B., Smit, D. J., Vaidya, B., et al. (2002). Osteonectin/SPARC induction by ectopic b3 integrin in human radial growth phase primary melanoma cells. Cancer Research, 62, 226–232.

    PubMed  CAS  Google Scholar 

  135. Kuphal, S., Palm, H. G., Poser, I., & Bosserhoff, A. K. (2005). Snail-regulated genes in malignant melanoma. Melanoma Research, 15(4), 305–313.

    PubMed  CAS  Google Scholar 

  136. Menon, P. M., Gutierrez, J. A., & Rempel, S. A. (2000). A study of SPARC and vitronectin localization and expression in pediatric and adult gliomas: High SPARC secretion correlates with decreased migration on vitronectin. International Journal of Oncology, 17(4), 683–693.

    PubMed  CAS  Google Scholar 

  137. Huang, H., Colella, S., Kurrer, M., Yonekawa, Y., Kleihues, P., & Ohgaki, H. (2000). Gene expression profiling of low-grade diffuse astrocytomas by cDNA arrays. Cancer Research, 60(24), 6868–6874.

    PubMed  CAS  Google Scholar 

  138. Rempel, S. A., Golembieski, W. A., Fisher, J. L., Maile, M., & Nakeff, A. (2001). SPARC modulates cell growth, attachment and migration of U87 glioma cells on brain extracellular matrix proteins. Journal of Neuro-oncology, 53, 149–160.

    PubMed  CAS  Google Scholar 

  139. Golembieski, W. A., & Rempel, S. A. (2002). cDNA array analysis of SPARC-modulated changes in glioma gene expression. Journal of Neuro-oncology, 60(3), 213–226.

    PubMed  Google Scholar 

  140. Zhou, X., Tan, F. K., Guo, X., Wallis, D., Milewicz, D. M., Xue, S., et al. (2005). Small interfering RNA inhibition of SPARC attenuates the profibrotic effect of transforming growth factor beta1 in cultured normal human fibroblasts. Arthritis and Rheumatism, 52(1), 257–261.

    PubMed  CAS  Google Scholar 

  141. Cantarella, G., Risuglia, N., Dell’eva, R., Lempereur, L., Albini, A., Pennisi, G., et al. (2006). TRAIL inhibits angiogenesis stimulated by VEGF expression in human glioblastoma cells. British Journal of Cancer, 94(10), 1428–1435.

    PubMed  CAS  Google Scholar 

  142. Kunigal, S., Gondi, C. S., Gujrati, M., Lakka, S. S., Dinh, D. H., Olivero, W. C., et al. (2006). SPARC-induced migration of glioblastoma cell lines via uPA-uPAR signaling and activation of small GTPase RhoA. International Journal of Oncology, 29(6), 1349–1357.

    PubMed  CAS  Google Scholar 

  143. Gagliano, N., Moscheni, C., Torri, C., Magnani, I., Bertelli, A. A., Nowicky, W., et al. (2006). Effect of Ukrain on matrix metalloproteinase-2 and secreted protein acidic and rich in cysteine (SPARC) expression in human glioblastoma cells. Anticancer Drugs, 17(2), 189–194.

    PubMed  CAS  Google Scholar 

  144. Colin, C., Baeza, N., Bartoli, C., Fina, F., Eudes, N., Nanni, I., et al. (2006). Identification of genes differentially expressed in glioblastoma versus pilocytic astrocytoma using suppression subtractive hybridization. Oncogene, 25(19), 2818–2826.

    PubMed  CAS  Google Scholar 

  145. Rempel, S. A., Ge, S., & Gutiérrez, J. A. (1999). SPARC: A potential diagnostic marker of invasive meningiomas. Clinical Cancer Research, 5, 237–241.

    PubMed  CAS  Google Scholar 

  146. Rich, J. N., Hans, C., Jones, B., Iversen, E. S., McLendon, R. E., Rasheed, B. K., et al. (2005). Gene expression profiling and genetic markers in glioblastoma survival. Cancer Research, 65(10), 4051–4058.

    PubMed  CAS  Google Scholar 

  147. Volmer, M. W., Radacz, Y., Hahn, S. A., Klein-Scory, S., Stuhler, K., Zapatka, M., et al. (2004). Tumor suppressor Smad4 mediates downregulation of the anti-adhesive invasion-promoting matricellular protein SPARC: Landscaping activity of Smad4 as revealed by a “secretome” analysis. Proteomics, 4(5), 1324–1334.

    PubMed  CAS  Google Scholar 

  148. Sansom, O. J., Mansergh, F. C., Evans, M. J., Wilkins, J. A., & Clarke, A. R. (2007). Deficiency of SPARC suppresses intestinal tumorigenesis in APCMin/+ mice. Gut, 56(10), 1410–1414.

    PubMed  CAS  Google Scholar 

  149. Madoz-Gurpide, J., Lopez-Serra, P., Martinez-Torrecuadrada, J. L., Sanchez, L., Lombardia, L., & Casal, J. I. (2006). Proteomics-based validation of genomic data: Applications in colorectal cancer diagnosis. Molecular & Cellular Proteomics, 5(8), 1471–1483.

    CAS  Google Scholar 

  150. Kaiser, S., Park, Y. K., Franklin, J. L., Halberg, R. B., Yu, M., Jessen, W. J., et al. (2007). Transcriptional recapitulation and subversion of embryonic colon development by mouse colon tumor models and human colon cancer. Genome Biology, 8, R131.

    PubMed  Google Scholar 

  151. Lecrone, V., Li, W., Devoll, R. E., Logothetis, C., & Farach-Carson, M. C. (2000). Calcium signals in prostate cancer cells: Specific activation by bone-matrix proteins. Cell Calcium, 27(1), 35–42.

    PubMed  CAS  Google Scholar 

  152. Thomas, R., True, L. D., Bassuk, J. A., Lange, P. H., & Vessella, R. L. (2000). Differential expression of osteonectin/SPARC during human prostate cancer progression. Clinical Cancer Research, 6(3), 1140–1149.

    PubMed  CAS  Google Scholar 

  153. Lapointe, J., Li, C., Higgins, J. P., van de Rijn, M., Bair, E., Montgomery, K., et al. (2004). Gene expression profiling identifies clinically relevant subtypes of prostate cancer. Proceedings of the National Academy of Sciences of the United States of America, 101(3), 811–816.

    PubMed  CAS  Google Scholar 

  154. Best, C. J., Gillespie, J. W., Yi, Y., Chandramouli, G. V., Perlmutter, M. A., Gathright, Y., et al. (2005). Molecular alterations in primary prostate cancer after androgen ablation therapy. Clinical Cancer Research, 11(19 Pt 1), 6823–6834.

    PubMed  CAS  Google Scholar 

  155. Kato, Y., Sakai, N., Baba, M., Kaneko, S., Kondo, K., Kubota, Y., et al. (1998). Stimulation of motility of human renal cell carcinoma by SPARC/Osteonectin/BM-40 associated with type IV collagen. Invasion Metastasis, 18(2), 105–114.

    PubMed  CAS  Google Scholar 

  156. Sakai, N., Baba, M., Nagasima, Y., Kato, Y., Hirai, K., Kondo, K., et al. (2001). SPARC expression in primary human renal cell carcinoma: Upregulation of SPARC in sarcomatoid renal carcinoma. Human Pathology, 32(10), 1064–1070.

    PubMed  CAS  Google Scholar 

  157. Gieseg, M. A., Cody, T., Man, M. Z., Madore, S. J., Rubin, M. A., & Kaldjian, E. P. (2002). Expression profiling of human renal carcinomas with functional taxonomic analysis. BMC Bioinformatics, 3, 26.

    PubMed  Google Scholar 

  158. Luo, A., Kong, J., Hu, G., Liew, C. C., Xiong, M., Wang, X., et al. (2004). Discovery of Ca2+-relevant and differentiation-associated genes downregulated in esophageal squamous cell carcinoma using cDNA microarray. Oncogene, 23(6), 1291–1299.

    PubMed  CAS  Google Scholar 

  159. Mitas, M., Almeida, J. S., Mikhitarian, K., Gillanders, W. E., Lewin, D. N., Spyropoulos, D. D., et al. (2005). Accurate discrimination of Barrett’s esophagus and esophageal adenocarcinoma using a quantitative three-tiered algorithm and multimarker real-time reverse transcription-PCR. Clinical Cancer Research, 11(6), 2205–2214.

    PubMed  CAS  Google Scholar 

  160. Che, Y., Luo, A., Wang, H., Qi, J., Guo, J., & Liu, Z. (2006). The differential expression of SPARC in esophageal squamous cell carcinoma. International Journal of Molecular Medicine, 17(6), 1027–1033.

    PubMed  CAS  Google Scholar 

  161. Porte, H., Triboulet, J. P., Kotelevets, L., Carrat, F., Prevot, S., Nordlinger, B., et al. (1998). Overexpression of stromelysin-3, BM-40/SPARC, and MET genes in human esophageal carcinoma: Implications for prognosis. Clinical Cancer Research, 4(6), 1375–1382.

    PubMed  CAS  Google Scholar 

  162. Yamashita, K., Upadhay, S., Mimori, K., Inoue, H., & Mori, M. (2003). Clinical significance of secreted protein acidic and rich in cystein in esophageal carcinoma and its relation to carcinoma progression. Cancer, 97(10), 2412–2419.

    PubMed  CAS  Google Scholar 

  163. Brabender, J., Marjoram, P., Lord, R. V., Metzger, R., Salonga, D., Vallbohmer, D., et al. (2005). The molecular signature of normal squamous esophageal epithelium identifies the presence of a field effect and can discriminate between patients with Barrett’s esophagus and patients with Barrett’s-associated adenocarcinoma. Cancer Epidemiology, Biomarkers & Prevention, 14(9), 2113–2117.

    CAS  Google Scholar 

  164. Siddiq, F., Sarkar, F. H., Wali, A., Pass, H. I., & Lonardo, F. (2004). Increased osteonectin expression is associated with malignant transformation and tumor associated fibrosis in the lung. Lung Cancer, 45(2), 197–205.

    PubMed  Google Scholar 

  165. De Vos, J., Thykjaer, T., Tarte, K., Ensslen, M., Raynaud, P., Requirand, G., et al. (2002). Comparison of gene expression profiling between malignant and normal plasma cells with oligonucleotide arrays. Oncogene, 21(44), 6848–6857.

    PubMed  Google Scholar 

  166. Hedvat, C. V., Comenzo, R. L., Teruya-Feldstein, J., Olshen, A. B., Ely, S. A., Osman, K., et al. (2003). Insights into extramedullary tumour cell growth revealed by expression profiling of human plasmacytomas and multiple myeloma. British Journal of Haematology, 122(5), 728–744.

    PubMed  CAS  Google Scholar 

  167. Martinez, N., Camacho, F. I., Algara, P., Rodriguez, A., Dopazo, A., Ruiz-Ballesteros, E., et al. (2003). The molecular signature of mantle cell lymphoma reveals multiple signals favoring cell survival. Cancer Research, 63(23), 8226–8232.

    PubMed  CAS  Google Scholar 

  168. Aouacheria, A., Navratil, V., Lopez-Perez, R., Gutierrez, N. C., Churkin, A., Barash, D., et al. (2007). In silico whole-genome screening for cancer-related single-nucleotide polymorphisms located in human mRNA untranslated regions. BMC Genomics, 8, 2.

    PubMed  Google Scholar 

  169. Bloomston, M., Ellison, E. C., Muscarella, P., Al-Saif, O., Martin, E. W., Melvin, W. S., et al. (2007). Stromal osteonectin overexpression is associated with poor outcome in patients with ampullary cancer. Annals of Surgical Oncology, 14(1), 211–217.

    PubMed  Google Scholar 

  170. Prenzel, K. L., Warnecke-Eberz, U., Xi, H., Brabender, J., Baldus, S. E., Bollschweiler, E., et al. (2006). Significant overexpression of SPARC/osteonectin mRNA in pancreatic cancer compared to cancer of the papilla of Vater. Oncology Reports, 15(5), 1397–1401.

    PubMed  CAS  Google Scholar 

  171. Le Bail, B., Faouzi, S., Boussarie, L., Guirouilh, J., Blanc, J. F., Carles, J., et al. (1999). Osteonectin/SPARC is overexpressed in human hepatocellular carcinoma. Journal of Pathology, 189(1), 46–52.

    PubMed  Google Scholar 

  172. Goldenberg, D., Ayesh, S., Schneider, T., Pappo, O., Jurim, O., Eid, A., et al. (2002). Analysis of differentially expressed genes in hepatocellular carcinoma using cDNA arrays. Molecular Carcinogenesis, 33, 113–124.

    PubMed  CAS  Google Scholar 

  173. Maeng, H. Y., Song, S. B., Choi, D. K., Kim, K. E., Jeong, H. Y., Sakaki, Y., et al. (2002). Osteonectin-expressing cells in human stomach cancer and their possible clinical significance. Cancer Letters, 184(1), 117–121.

    PubMed  CAS  Google Scholar 

  174. Inoue, H., Matsuyama, A., Mimori, K., Ueo, H., & Mori, M. (2002). Prognostic score of gastric cancer determined by cDNA microarray. Clinical Cancer Research, 8(11), 3475–3479.

    PubMed  CAS  Google Scholar 

  175. Wang, C. S., Lin, K. H., Chen, S. L., Chan, Y. F., & Hsueh, S. (2004). Overexpression of SPARC gene in human gastric carcinoma and its clinic–pathologic significance. British Journal of Cancer, 91(11), 1924–1930.

    PubMed  CAS  Google Scholar 

  176. Paley, P. J., Goff, B. A., Gown, A. M., Greer, B. E., & Sage, E. H. (2000). Alterations in SPARC and VEGF immunoreactivity in epithelial ovarian cancer. Gynecologic Oncology, 78(3 Pt 1), 336–341.

    PubMed  CAS  Google Scholar 

  177. Nimphius, W., Moll, R., Olbert, P., Ramaswamy, A., & Barth, P. J. (2007). CD34+ fibrocytes in chronic cystitis and noninvasive and invasive urothelial carcinomas of the urinary bladder. Virchows Archiv, 450(2), 179–185.

    PubMed  CAS  Google Scholar 

  178. Yamanaka, M., Kanda, K., Li, N.-C., Fukumori, T., Oka, N., Kanayama, H.-O., et al. (2001). Analysis of the gene expression of SPARC and its prognostic value for bladder cancer. Journal of Urology, 166, 2495–2499.

    PubMed  CAS  Google Scholar 

  179. Chen, Y., Miller, C., Mosher, R., Zhao, X., Deeds, J., Morrissey, M., et al. (2003). Identification of cervical cancer markers by cDNA and tissue microarrays. Cancer Research, 63(8), 1927–1935.

    PubMed  CAS  Google Scholar 

  180. Sova, P., Feng, Q., Geiss, G., Wood, T., Strauss, R., Rudolf, V., et al. (2006). Discovery of novel methylation biomarkers in cervical carcinoma by global demethylation and microarray analysis. Cancer Epidemiology, Biomarkers & Prevention, 15(1), 114–123.

    CAS  Google Scholar 

  181. Rodriguez-Jimenez, F. J., Caldes, T., Iniesta, P., Vidart, J. A., Garcia-Asenjo, J. L., & Benito, M. (2007). Overexpression of SPARC protein contrasts with its transcriptional silencing by aberrant hypermethylation of SPARC CpG-rich region in endometrial carcinoma. Oncology Reports, 17(6), 1301–1307.

    PubMed  CAS  Google Scholar 

  182. Fanburg-Smith, J. C., Bratthauer, G. L., & Miettinen, M. (1999). Osteocalcin and osteonectin immunoreactivity in extraskeletal osteosarcoma: A study of 28 cases. Human Pathology, 30(1), 32–38.

    PubMed  CAS  Google Scholar 

  183. Dalla-Torre, C. A., Yoshimoto, M., Lee, C. H., Joshua, A. M., de Toledo, S. R., Petrilli, A. S., et al. (2006). Effects of THBS3, SPARC and SPP1 expression on biological behavior and survival in patients with osteosarcoma. BMC Cancer, 6(1), 237.

    PubMed  Google Scholar 

  184. Takano, T., Hasegawa, Y., Miyauchi, A., Matsuzuka, F., Yoshida, H., Kuma, K., et al. (2002). Quantitative analysis of osteonectin mRNA in thyroid carcinomas. Endocrine Journal, 49(4), 511–516.

    PubMed  CAS  Google Scholar 

  185. Chin, D., Boyle, G. M., Williams, R. M., Ferguson, K., Pandeya, N., Pedley, J., et al. (2005). Novel markers for poor prognosis in head and neck cancer. International Journal of Cancer, 113(5), 789–797.

    CAS  Google Scholar 

  186. Aycock, R. L., Bradshaw, A. C., Sage, E. H., & Starcher, B. (2004). Development of UV-induced squamous cell carcinomas is suppressed in the absence of SPARC. Journal of Investigative Dermatology, 123(3), 592–599.

    PubMed  CAS  Google Scholar 

  187. Said, N., Najwer, I., & Motamed, K. (2007). Secreted protein acidic and rich in cysteine (SPARC) inhibits integrin-mediated adhesion and growth factor-dependent survival signaling in ovarian cancer. American Journal of Pathology, 170(3), 1054–1063.

    PubMed  CAS  Google Scholar 

  188. Cody, N. A., Ouellet, V., Manderson, E. N., Quinn, M. C., Filali-Mouhim, A., Tellis, P., et al. (2007). Transfer of chromosome 3 fragments suppresses tumorigenicity of an ovarian cancer cell line monoallelic for chromosome 3p. Oncogene, 26(4), 618–632.

    PubMed  CAS  Google Scholar 

  189. Dhanesuan, N., Sharp, J. A., Blick, T., Price, J. T., & Thompson, E. W. (2002). Doxycycline-inducible expression of SPARC/Osteonectin/BM40 in MDA-MB-231 human breast cancer cells results in growth inhibition. Breast Cancer Research and Treatment, 75(1), 73–85.

    PubMed  CAS  Google Scholar 

  190. Bergamaschi, A., Tagliabue, E., Sorlie, T., Naume, B., Triulzi, T., Orlandi, R., et al. (2007). Extracellular matrix signature identifies breast cancer subgroups with different clinical outcome. Journal of Pathology, 214(3), 357–367.

    Google Scholar 

  191. Tang, H., Wang, J., Bai, F., Hong, L., Liang, J., Gao, J., et al. (2007). Inhibition of osteopontin would suppress angiogenesis in gastric cancer. Biochemistry and Cell Biology, 85(1), 103–110.

    PubMed  CAS  Google Scholar 

  192. Chlenski, A., Liu, S., Guerrero, L. J., Yang, Q., Tian, Y., Salwen, H. R., et al. (2006). SPARC expression is associated with impaired tumor growth, inhibited angiogenesis and changes in the extracellular matrix. International Journal of Cancer, 118(2), 310–316.

    CAS  Google Scholar 

  193. Chlenski, A., Guerrero, L. J., Yang, Q., Tian, Y., Peddinti, R., Salwen, H. R., et al. (2007). SPARC enhances tumor stroma formation and prevents fibroblast activation. Oncogene, 26(31), 4513–4522.

    PubMed  CAS  Google Scholar 

  194. Puolakkainen, P., Bradshaw, A. D., Kyriakides, T. R., Reed, M., Brekken, R., Wight, T., et al. (2003). Compromised production of extracellular matrix in mice lacking secreted protein, acidic and rich in cysteine (SPARC) leads to a reduced foreign body reaction to implanted biomaterials. American Journal of Pathology, 162(2), 627–635.

    PubMed  CAS  Google Scholar 

  195. DiMartino, J. F., Lacayo, N. J., Varadi, M., Li, L., Saraiya, C., Ravindranath, Y., et al. (2006). Low or absent SPARC expression in acute myeloid leukemia with MLL rearrangements is associated with sensitivity to growth inhibition by exogenous SPARC protein. Leukemia, 20(3), 426–432.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We want to acknowledge the national and international agencies that supported the work, such as the National Agency for Promotion of Science and Technology, the Ministry of Health, the National Council of Scientific and Technological Research (Argentina), and the Wellcome Trust and the Agency for International Cancer Research, (United Kingdom). We also wish to acknowledge the continuous support of the Fundación Rene Baron and Amigos de la Fundación Leloir para la Investigación contra el Cáncer (AFULIC), Argentina.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Osvaldo L. Podhajcer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Podhajcer, O.L., Benedetti, L.G., Girotti, M.R. et al. The role of the matricellular protein SPARC in the dynamic interaction between the tumor and the host. Cancer Metastasis Rev 27, 691–705 (2008). https://doi.org/10.1007/s10555-008-9146-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10555-008-9146-7

Keywords

Navigation