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Targeting Cancer Stem Cells to Modulate Alternative Vascularization Mechanisms

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Abstract

Recently, many papers have shown that tumor vascularization can be explained by angiogenesis, recruitment, cooption, vasculogenic mimicry and by mosaic vessels. In particular, vasculogenic mimicry seems to be different from mosaic blood vessels, where tumor cells form a part of the surface of the vessel while the remaining part is covered by endothelium. In this case, tumor cells in apparent contact with the lumen do not show an endothelial phenotype. More recently, vasculogenic mimicry was proposed to occur in patients with multiple myeloma due to bone marrow macrophages. Herein, all these data are, for the first time, discussed critically in comparison to cancer stem cells—which show high trans-differentiative capacity—and bone-marrow derived stem cells. In fact, the presence of alternative vasculogenic patterns might be due to the presence of stem cell population (cancer stem cells or bone-marrow stem cells). In this connection, the literature is discussed extensively and possible models are proposed. Pharmacological perspectives will also discuss.

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References

  1. Monzani, E., Facchetti, F., Galmozzi, E., Corsini, E., Benetti, A., Cavazzin, C., et al. (2007). Melanoma contains CD133 and ABCG2 positive cells with enhanced tumourigenic potential. European Journal of Cancer, 43, 935–946.

    Article  PubMed  CAS  Google Scholar 

  2. Klein, W. M., Wu, B. P., Zhao, S., Wu, H., Klein-Szanto, A. J., & Tahan, S. R. (2007). Increased expression of stem cell markers in malignant melanoma. Modern Pathology, 20, 102–107.

    Article  PubMed  CAS  Google Scholar 

  3. La Porta, C. A. (2007). Drug resistance in melanoma: new perspectives. Current Medicinal Chemistry, 14, 387–391.

    Article  PubMed  Google Scholar 

  4. Holash, J., Maisonpierre, P. C., Compton, D., Boland, P., Alexander, C. R., Zagzag, D., et al. (1999). Vessel cooption, regression and growth in tumors mediated by angiopoietins and VEGF. Science, 284, 1994–1998.

    Article  PubMed  CAS  Google Scholar 

  5. Zhang, L., Yang, N., Park, J. W., Katsaros, D., Fracchioli, S., Cao, G., et al. (2003). Tumor-derived vascular endothelial growth factor up-regulates angiopoietin-2 in host endothelium and destabilizes host vasculature, supporting angiogenesis in ovarian cancer. Cancer Research, 63, 3403–3412.

    PubMed  CAS  Google Scholar 

  6. Dome, B., Paku, S., Somlai, B., & Timar, J. (2002). Vascularization of cutaneous melanoma involves vessel co-option and has clinical significance. The Journal of Pathology, 197, 355–362.

    Article  PubMed  Google Scholar 

  7. Kim, E. S., Serur, A., Huang, J., Manley, C. A., McCrudden, K. W., Frischer, J. S., et al. (2002). Potent VEGF blockade causes regression of coopted vessels in a model of neuroblastoma. Proceedings of the National Academy of Sciences of the United States of America, 99, 11399–11404.

    Article  PubMed  CAS  Google Scholar 

  8. Hillen, F., & Griffioen, A. W. (2007). Tumour vascularization: sprouting angiogenesis and beyond. Cancer Metastasis Reviews, 26, 489–502.

    Article  PubMed  Google Scholar 

  9. Paku, S., Kopper, L., & Nagy, P. (2005). Development of the vasculature in “pushing-type” liver metastases of an experimental colorectal cancer. International Journal of Cancer, 115, 893–902.

    Article  CAS  Google Scholar 

  10. Maisonpierre, P. C., Suri, C., Jones, P. F., Bartunkova, S., Wiegand, S. J., Radziejewski, C., et al. (1997). Angiopoietin-2, a Natural Antagonist for Tie-2 That Disrupts in vivo Angiogenesis. Science, 277, 55–60.

    Article  PubMed  CAS  Google Scholar 

  11. Burri, P. H., Hlushchuk, R., & Djonov, V. (2004). Intussusceptive angiogenesis: Its emergence, its characteristics, and its significance. Developmental Dynamics, 231, 474–488.

    Article  PubMed  Google Scholar 

  12. Nagy, J. A., Morgan, E. S., Herzberg, K. T., Manseau, E. J., Dvorak, A. M., & Dvorak, H. F. (1995). Pathogenesis of ascites tumor growth: angiogenesis, vascular remodeling and stroma formation in the peritoneal lining. Cancer Research, 55, 376–385.

    PubMed  CAS  Google Scholar 

  13. Patan, S., Munn, L. L., & Jain, R. K. (1996). Intussusceptive microvascular growth in a human colon adenocarcinoma xenograft: a novel mechanism of tumor angiogenesis. Microvascular Research, 51, 260–272.

    Article  PubMed  CAS  Google Scholar 

  14. Burri, P. H., & Djonov, V. (2002). Intussusceptive angiogenesis––the alternative to capillary sprouting. Molecular Aspects of Medicine, 23, S1–S27.

    Article  PubMed  Google Scholar 

  15. Folkman, J., & D’Amore, P. A. (1996). Blood vessel formation: what is its molecular basis? Cell, 87, 1153–1155.

    Article  PubMed  CAS  Google Scholar 

  16. Hellstrom, M., Kalen, M., Lindahl, P., Abramsson, A., & Betsholtz, C. (1999). Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development, 126, 3047–3055.

    PubMed  CAS  Google Scholar 

  17. Shyy, Y. J., Hsieh, H. J., Usami, S., & Chien, S. (1994). Fluid shear stress induces a biphasic response of human monocyte chemotactic protein 1 gene expression in vascular endothelium. Proceedings of the National Academy of Sciences of the United States of America, 91, 4678–4682.

    Article  PubMed  CAS  Google Scholar 

  18. Gale, N. W., Baluk, P., Pan, L., Kwan, M., Holash, J., DeChiara, T. M., et al. (2001). Ephrin-B2 selectively marks arterial vessels and neovascularization sites in the adult, with expression in both endothelial and smooth-muscle cells. Developmental Biology, 230, 151–160.

    Article  PubMed  CAS  Google Scholar 

  19. Döme, B., Hendrix, M. J., Paku, S., Tóvári, J., & Tímár, J. (2007). Alternative vascularization mechanisms in cancer: pathology and therapeutic implications. The American Journal of Pathology, 170, 1–15.

    Article  PubMed  CAS  Google Scholar 

  20. Zengin, E., Chalajour, F., Gehling, U. M., Ito, W. D., Treede, H., Lauke, H., et al. (2006). Vascular wall resident progenitor cells: a source for postnatal vasculogenesis. Development, 133, 1543–1551.

    Article  PubMed  CAS  Google Scholar 

  21. Asahara, T., Murohara, T., Sullivan, A., Kalka, C., Pastore, C., Silver, M., et al. (1997). Isolation of putative progenitor endothelial cells for angiogenesis. Science, 275, 964–967.

    Article  PubMed  CAS  Google Scholar 

  22. Kalka, C., Masuda, H., Takahashi, T., Kalka-Moll, W. M., Silver, M., Kearney, M., et al. (2000). Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proceedings of the National Academy of Sciences of the United States of America, 97, 3422–3427.

    Article  PubMed  CAS  Google Scholar 

  23. Ribatti, D. (2004). The involvement of endothelial progenitor cells in tumour angiogenesis. Journal of Cellular and Molecular Medicine, 8, 294–300.

    Article  PubMed  CAS  Google Scholar 

  24. Asahara, T., Masuda, H., Takahashi, T., Kalka, C., Pastore, C., Silver, M., et al. (1999). Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circulation Research, 85, 221–228.

    PubMed  CAS  Google Scholar 

  25. Hattori, K., Dias, S., Heissig, B., Hackett, N. R., Lyden, D., Tateno, M., et al. (2001). Vascular endothelial growth factor and angiopoietin-1 stimulate postnatal hematopoiesis by recruitment of vasculogenic and hematopoietic stem cells. The Journal of Experimental Medicine, 193, 1005–1014.

    Article  PubMed  CAS  Google Scholar 

  26. Iwaguro, H., Yamaguchi, J., Kalka, C., Murasawa, S., Masuda, H., Hayashi, S., et al. (2002). Endothelial progenitor cell vascular endothelial growth factor gene transfer for vascular regeneration. Circulation, 105, 732–738.

    Article  PubMed  CAS  Google Scholar 

  27. Gill, M., Dias, K., Hattori, M. L., Rivera, D., Hicklin, L., Witte, L., et al. (2001). Vascular trauma induces rapid but transient mobilization of VEGFR2(+) AC133(+) endothelial precursor cells. Circulation Research, 88, 167–174.

    PubMed  CAS  Google Scholar 

  28. Lyden, D., Hattori, K., Dias, S., Costa, C., Blaikie, P., Butros, L., et al. (2001). Impaired recruitment of bone marrow derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nature Medicine, 7, 1194–1201.

    Article  PubMed  CAS  Google Scholar 

  29. Bolontrade, M. F., Zhou, R. R., & Kleinerman, E. S. (2002). Vasculogenesis plays a role in the growth of Ewing’s sarcoma in vivo. Clinical Cancer Research, 8, 3622–3627.

    PubMed  Google Scholar 

  30. Shirakawa, K., Furuhata, S., Watanabe, I., Hayase, H., Shimizu, A., Ikarashi, Y., et al. (2002). Induction of vasculogenesis in breast cancer models. British Journal of Cancer, 87, 1454–1461.

    Article  PubMed  CAS  Google Scholar 

  31. Capillo, M., Mancuso, P., Gobbi, A., Monestiroli, S., Pruneri, G., Dell’Agnola, C., et al. (2003). Continuous infusion of endostatin inhibits differentiation, mobilization, and clonogenic potential of endothelial cell progenitors. Clinical Cancer Research, 9, 377–382.

    PubMed  CAS  Google Scholar 

  32. Pettersson, A., Nagy, J. A., Brown, L. F., Sundberg, C., Morgan, E., Jungles, S., et al. (2000). Heterogeneity of the angiogenic response induced in different normal adult tissues by vascular permeability factor/vascular endothelial growth factor. Laboratory Investigation, 80, 99–115.

    Article  PubMed  CAS  Google Scholar 

  33. Wesseling, P., Vandersteenhoven, J. J., Downey, B. T., Ruiter, D. J., & Burger, P. C. (1993). Cellular components of microvascular proliferation in human glial and metastatic brain neoplasms. A light microscopic and immunohistochemical study of formalin-fixed, routinely processed material. Acta Neuropathologica, 85, 508–514.

    Article  PubMed  CAS  Google Scholar 

  34. Straume, O., Chappuis, P. O., Salvesen, H. B., Halvorsen, O. J., Haukaas, S. A., Goffin, J. R., et al. (2002). Prognostic importance of glomeruloid microvascular proliferation indicates an aggressive angiogenic phenotype in human cancers. Cancer Research, 62, 6808–6811.

    PubMed  CAS  Google Scholar 

  35. Brat, D. J., Castellano-Sanchez, A., Kaur, B., & Van Meir, E. G. (2002). Genetic and biologic progression in astrocytomas and their relation angiogenic dysregulation. Advances in Anatomic Pathology, 9, 24–36.

    Article  PubMed  Google Scholar 

  36. Straume, O., & Akslen, L. A. (2003). Increased expression of VEGF-receptors (FLT-1, KDR, NRP-1) and thrombospondin-1 is associated with glomeruloid microvascular proliferation, an aggressive angiogenic phenotype, in malignant melanoma. Angiogenesis, 6, 295–301.

    Article  PubMed  CAS  Google Scholar 

  37. Maniotis, A. J., Folberg, R., Hess, A., Seftor, E. A., Gardner, L. M., Pe'er, J., et al. (1999). Vascular channel formation by human melanoma cells in vivo and in vitro, vasculogenic mimicry. The American Journal of Pathology, 155, 739–752.

    PubMed  CAS  Google Scholar 

  38. Hendrix, M. J., Seftor, E. A., Hess, A. R., & Seftor, R. E. (2003). Vasculogenic mimicry and tumor cell plasticity: lessons from melanoma. Nature Reviews Cancer, 3, 411–421.

    Article  PubMed  CAS  Google Scholar 

  39. Seftor, E. A., Meltzer, P. S., Schatteman, G. C., Gruman, L. M., Hess, A. R., Kirschmann, D. A., et al. (2002). Expression of multiple molecular phenotypes by aggressive melanoma tumor cells: role in vasculogenic mimicry. Critical Reviews in Oncology/hematology, 44, 17–27.

    Article  PubMed  Google Scholar 

  40. Hendrix, M. J., Seftor, E. A., Hess, A. R., & Seftor, R. E. (2003). Molecular plasticity of human melanoma cells. Oncogene, 22, 3070–3075.

    Article  PubMed  CAS  Google Scholar 

  41. Folberg, R., Rummelt, V., Parys-Van Ginderdeuren, R., Hwang, T., Woolson, R. F., & Pe’er, J., et al. (1993). The prognostic value of tumor blood vessel morphology in primary uveal melanoma. Ophthalmology, 100, 1389–1398.

    PubMed  CAS  Google Scholar 

  42. Makitie, T., Summanen, P., Tarkkanen, A., & Kivela, T. (1999). Microvascular loops and networks as prognostic indicators in choroidal and ciliary body melanomas. Journal of National Cancer Institute, 91, 359–367.

    Article  CAS  Google Scholar 

  43. Sakamoto, T., Sakamoto, M., Yoshikawa, H., Hata, Y., Ishibashi, T., Ohnishi, Y., et al. (1996). Histologic findings and prognosis of uveal malignant melanoma in Japanese patients. American Journal of Ophthalmology, 121, 276–283.

    PubMed  CAS  Google Scholar 

  44. Seregard, S., Spangberg, B., Juul, C., & Oskarsson, M. (1998). Prognostic accuracy of the mean of the largest nucleoli, vascular patterns, and PC-10 in posterior uveal melanoma. Ophthalmology, 105, 485–491.

    Article  PubMed  CAS  Google Scholar 

  45. Thies, A., Mangold, U., Moll, I., & Schumacher, U. (2001). PAS-positive loops and networks as a prognostic indicator in cutaneous malignant melanoma. The Journal of Pathology, 195, 537–542.

    Article  PubMed  CAS  Google Scholar 

  46. Warso, M. A., Maniotis, A. J., Chen, X., Majumdar, D., Patel, M. K., & Shilkaitis, A., et al. (2001). Prognostic significance of periodic acid-Schiff-positive patterns in primary cutaneous melanoma. Clinical Cancer Research, 7, 473–477.

    PubMed  CAS  Google Scholar 

  47. Rummelt, V., Mehaffey, M. G., Campbell, R. J., Pe’er, J., Bentler, S. E., & Woolson, R. F., et al. (1998). Microcirculation architecture of metastases from primary ciliary body and choroidal melanomas. American Journal of Ophthalmology, 126, 303–305.

    Article  PubMed  CAS  Google Scholar 

  48. Shirakawa, K., Kobayashi, H., Heike, Y., Kawamoto, S., Brechbiel, M. W., & Kasumi, F., et al. (2002). Hemodynamics in vasculogenic mimicry and angiogenesis of inflammatory breast cancer xenograft. Cancer Research, 62, 560–566.

    PubMed  CAS  Google Scholar 

  49. Zhou, Y., Fisher, S. J., Janatpour, M., Genbacev, O., Dejana, E., Wheelock, M., et al. (1997). Human cytotrophoblasts adopt a vascular phenotype as they differentiate. A strategy for successful endovascular invasion. The Journal of Clinical Investigation, 99, 2139–2151.

    Article  PubMed  CAS  Google Scholar 

  50. Chang, Y. S., di Tomaso, E., Mc Donald, D. M., Jones, R., Jain, R. K., & Munn, L. L. (2000). Mosaic blood vessels in tumors: frequency of cancer cells in contact with flowing blood. Proceedings of the National Academy of Sciences of the United States of America, 97, 14608–14613.

    Article  PubMed  CAS  Google Scholar 

  51. Zhang, S., Guo, H., Zhang, D., Zhang, W., Zhao, X., Ren, Z., et al. (2006). Microcirculation patterns in different stages of melanoma growth. Oncology Reports, 15, 15–20.

    PubMed  CAS  Google Scholar 

  52. Nicosia, R. F., & Ottinetti, A. (1990). Growth of microvessels in serum-free matrix culture of rat aorta. A quantitative assay of angiogenesis in vitro. Laboratory Investigation, 63, 115–122.

    PubMed  CAS  Google Scholar 

  53. Scavelli, C., Nico, B., Cirulli, T., Ria, R., Di Pietro, G., Mangieri, D., et al. (2007). A vasculogenic mimicry by bone marrow macrophages in patients with multiple myeloma. Oncogene, 30, 1–12.

    Google Scholar 

  54. Sozzani, S., Rusnati, M., Riboldi, E., Mitola, S., & Presta, M. (2007). Dendritic cell-endothelial cell cross-talk in angiogenesis. Trends in Immunology, 28, 385–392.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

We thank Riccardo Bazzotti for the relevant contribution to the vasculogenic mimicry picture.

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  1. Molecular Oncology Laboratory, Department of Biomolecular Science and Biotechnology, University of Milan, 20133, Milan, Italy

    Elena Monzani & Caterina AM La Porta

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  1. Elena Monzani
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  2. Caterina AM La Porta
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Correspondence to Caterina AM La Porta.

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Monzani, E., La Porta, C.A. Targeting Cancer Stem Cells to Modulate Alternative Vascularization Mechanisms. Stem Cell Rev 4, 51–56 (2008). https://doi.org/10.1007/s12015-008-9009-1

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