Skip to main content

Advertisement

Log in

Functional analysis of tumor metastasis: modeling colon cancer

  • Review
  • Published:
Oncology Reviews

Abstract

The primary cause of death from colon cancer results from metastases that withstand conventional therapy and escape locoregional control. The molecular regulation of the tumor cell’s acquired ability for invasion and metastasis is still not completely understood and progress in this field may generate novel therapeutic targets. Osteopontin (OPN) has recently been identified as a lead marker for colon cancer progression with elevated OPN expression correlating with advanced stage and poor survival. This key regulator of metastasis has been shown to induce invasive mechanisms, increase motility, adhesiveness, angiogenesis, and enhance evasion of the immune system to augment the metastatic potential in colon cancer cells. This review will discuss the basic mechanisms underlying tumor metastasis, recent innovations used to screen and identify metastatic genes in colon cancer, and model systems used to analyze these potential targets. Target genes associated with activation of OPN, a master regulator of tumor metastasis, will be described in the context of a colon cancer model. Finally, the innovative techniques of RNA interference and aptamer technology for targeting metastasis genes will be reviewed.

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.

Similar content being viewed by others

References

  1. Sporn MB (1996) The war on cancer. Lancet 347:1377–1381

    Article  PubMed  CAS  Google Scholar 

  2. Jemal A, Siegel R, Ward E (2007) Cancer statistics, 2007. CA Cancer J Clin 57:43–66

    Article  PubMed  Google Scholar 

  3. Fidler IJ (1990) Critical factors in the biology of human cancer metastasis: twenty-eighth G.H.A. Clowes memorial award lecture. Cancer Res 50:6130–6138

    PubMed  CAS  Google Scholar 

  4. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    Article  PubMed  CAS  Google Scholar 

  5. Martin R, Paty P, Fong Y (2003) Simultaneous liver and colorectal resections are safe for synchronous colorectal liver metastasis. J Am Coll Surg 197:233–241; discussion 241–242

    Article  PubMed  Google Scholar 

  6. Scheele J, Stangl R, Altendorf-Hofmann A, Gall FP (1991) Indicators of prognosis after hepatic resection for colorectal secondaries. Surgery 110:13–29

    PubMed  CAS  Google Scholar 

  7. Kinzler KW, Vogelstein B (1996) Lessons from hereditary colorectal cancer. Cell 87:159–170

    Article  PubMed  CAS  Google Scholar 

  8. Welch DR, Steeg PS, Rinker-Schaeffer CW (2000) Molecular biology of breast cancer metastasis. Genetic regulation of human breast carcinoma metastasis. Breast Cancer Res 2:408–416

    Article  PubMed  CAS  Google Scholar 

  9. Guo W, Giancotti FG (2004) Integrin signalling during tumour progression. Nat Rev Mol Cell Biol 5:816–826

    Article  PubMed  CAS  Google Scholar 

  10. Liotta LA, Steeg PS, Stetler-Stevenson WG (1991) Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 64:327–336

    Article  PubMed  CAS  Google Scholar 

  11. Fidler IJ (2003) The pathogenesis of cancer metastasis: the ’seed and soil’ hypothesis revisited. Nat Rev Cancer 3:453–458

    Article  PubMed  CAS  Google Scholar 

  12. Paget S (1989) The distribution of secondary growths in cancer of the breast. Cancer Metastasis Rev 8:98–101

    PubMed  CAS  Google Scholar 

  13. Kuo TH, Kubota T, Watanabe M et al (1995) Liver colonization competence governs colon cancer metastasis. Proc Natl Acad Sci U S A 92:12085–12089

    Article  PubMed  CAS  Google Scholar 

  14. Morikawa K, Walker SM, Nakajima M et al (1988) Influence of organ environment on the growth, selection, and metastasis of human colon carcinoma cells in nude mice. Cancer Res 48:6863–6871

    PubMed  CAS  Google Scholar 

  15. Agrawal D, Chen T, Irby R et al (2002) Osteopontin identified as lead marker of colon cancer progression, using pooled sample expression profiling. J Natl Cancer Inst 94:513–521

    PubMed  CAS  Google Scholar 

  16. Yeatman TJ, Chambers AF (2003) Osteopontin and colon cancer progression. Clin Exp Metastasis 20:85–90

    Article  PubMed  CAS  Google Scholar 

  17. Huang ES, Nevins JR, West M, Kuo PC (2004) An overview of genomic data analysis. Surgery 136:497–499

    Article  PubMed  Google Scholar 

  18. Bertucci F, Salas S, Eysteries S et al (2004) Gene expression profiling of colon cancer by DNA microarrays and correlation with histoclinical parameters. Oncogene 23:1377–1391

    Article  PubMed  CAS  Google Scholar 

  19. Li M, Lin YM, Hasegawa S et al (2004) Genes associated with liver metastasis of colon cancer, identified by genome-wide cDNA microarray. Int J Oncol 24:305–312

    PubMed  Google Scholar 

  20. Williams NS, Gaynor RB, Scoggin S et al (2003) Identification and validation of genes involved in the pathogenesis of colorectal cancer using cDNA microarrays and RNA interference. Clin Cancer Res 9:931–946

    PubMed  CAS  Google Scholar 

  21. Kitahara O, Furukawa Y, Tanaka T et al (2001) Alterations of gene expression during colorectal carcinogenesis revealed by cDNA microarrays after laser-capture microdissection of tumor tissues and normal epithelia. Cancer Res 61:3544–3549

    PubMed  CAS  Google Scholar 

  22. Li A, Varney ML, Singh RK (2004) Constitutive expression of growth regulated oncogene (gro) in human colon carcinoma cells with different metastatic potential and its role in regulating their metastatic phenotype. Clin Exp Metastasis 21:571–579

    Article  PubMed  CAS  Google Scholar 

  23. Gavert N, Sheffer M, Raveh S et al (2007) Expression of L1-CAM and ADAM10 in human colon cancer cells induces metastasis. Cancer Res 67:7703–7712

    Article  PubMed  CAS  Google Scholar 

  24. Huerta S, Harris DM, Jazirehi A et al (2003) Gene expression profile of metastatic colon cancer cells resistant to cisplatin-induced apoptosis. Int J Oncol 22:663–670

    PubMed  CAS  Google Scholar 

  25. Friedman DB, Hill S, Keller JW et al (2004) Proteome analysis of human colon cancer by two-dimensional difference gel electrophoresis and mass spectrometry. Proteomics 4:793–811

    Article  PubMed  CAS  Google Scholar 

  26. Tachibana M, Ohkura Y, Kobayashi Y et al (2003) Expression of apolipoprotein A1 in colonic adenocarcinoma. Anticancer Res 23:4161–4167

    PubMed  CAS  Google Scholar 

  27. Le Naour F, Andre M, Greco C et al (2006) Profiling of the tetraspanin web of human colon cancer cells. Mol Cell Proteomics 5:845–857

    Article  PubMed  CAS  Google Scholar 

  28. Ruginis T, Taglia L, Matusiak D et al (2006) Consequence of gastrin-releasing peptide receptor activation in a human colon cancer cell line: a proteomic approach. J Proteome Res 5:1460–1468

    Article  PubMed  CAS  Google Scholar 

  29. Swearingen ML, Sun D, Bourner M, Weinstein EJ (2003) Detection of differentially expressed HES-6 gene in metastatic colon carcinoma by combination of suppression subtractive hybridization and cDNA library array. Cancer Lett 198:229–239

    Article  PubMed  CAS  Google Scholar 

  30. Nakagawa H, Liyanarachchi S, Davuluri RV et al (2004) Role of cancer-associated stromal fibroblasts in metastatic colon cancer to the liver and their expression profiles. Oncogene 23: 7366–7377

    Article  PubMed  CAS  Google Scholar 

  31. Sugiyama Y, Farrow B, Murillo C et al (2005) Analysis of differential gene expression patterns in colon cancer and cancer stroma using microdissected tissues. Gastroenterology 128:480–486

    Article  PubMed  CAS  Google Scholar 

  32. Debies MT, Welch DR (2001) Genetic basis of human breast cancer metastasis. J Mammary Gland Biol Neoplasia 6:441–451

    Article  PubMed  CAS  Google Scholar 

  33. Fidler IJ, Radinsky R (1990) Genetic control of cancer metastasis. J Natl Cancer Inst 82:166–168

    Article  PubMed  CAS  Google Scholar 

  34. Gavert N, Conacci-Sorrell M, Gast D et al (2005) L1, a novel target of beta-catenin signaling, transforms cells and is expressed at the invasive front of colon cancers. J Cell Biol 168:633–642

    Article  PubMed  CAS  Google Scholar 

  35. Irby RB, McCarthy SM, Yeatman TJ (2004) Osteopontin regulates multiple functions contributing to human colon cancer development and progression. Clin Exp Metastasis 21:515–523

    Article  PubMed  CAS  Google Scholar 

  36. Sattler M, Quackenbush E, Salgia R (2003) Cell motility, adhesion, homing, and migration assays in the studies of tyrosine kinases. Methods Mol Med 85:87–105

    PubMed  CAS  Google Scholar 

  37. Albini A, Iwamoto Y, Kleinman HK et al (1987) A rapid in vitro assay for quantitating the invasive potential of tumor cells. Cancer Res 47:3239–3245

    PubMed  CAS  Google Scholar 

  38. Shaw LM (2005) Tumor cell invasion assays. Methods Mol Biol 294:97–105

    PubMed  Google Scholar 

  39. Hamburger AW, Salmon SE (1977) Primary bioassay of human tumor stem cells. Science 197:461–463

    Article  PubMed  CAS  Google Scholar 

  40. Khanna C, Hunter K (2005) Modeling metastasis in vivo. Carcinogenesis 26:513–523

    Article  PubMed  CAS  Google Scholar 

  41. Morikawa K, Walker SM, Jessup JM, Fidler IJ (1988) In vivo selection of highly metastatic cells from surgical specimens of different primary human colon carcinomas implanted into nude mice. Cancer Res 48:1943–1948

    PubMed  CAS  Google Scholar 

  42. Giavazzi R, Campbell DE, Jessup JM et al (1986) Metastatic behavior of tumor cells isolated from primary and metastatic human colorectal carcinomas implanted into different sites in nude mice. Cancer Res 46:1928–1933

    PubMed  CAS  Google Scholar 

  43. Reeder JA, Gotley DC, Walsh MD et al (1998) Expression of antisense CD44 variant 6 inhibits colorectal tumor metastasis and tumor growth in a wound environment. Cancer Res 58:3719–3726

    PubMed  CAS  Google Scholar 

  44. Kitakata H, Nemoto-Sasaki Y, Takahashi Y et al (2002) Essential roles of tumor necrosis factor receptor p55 in liver metastasis of intrasplenic administration of colon 26 cells. Cancer Res 62:6682–6687

    PubMed  CAS  Google Scholar 

  45. Tan MH, Holyoke ED, Goldrosen MH (1977) Murine colon adenocarcinoma: syngeneic orthotopic transplantation and subsequent hepatic metastases. J Natl Cancer Inst 59:1537–1544

    PubMed  CAS  Google Scholar 

  46. Ozawa S, Lu W, Bucana CD et al (2003) Regression of primary murine colon cancer and occult liver metastasis by intralesional injection of lyophilized preparation of insect cells producing murine interferon-beta. Int J Oncol 22:977–984

    PubMed  CAS  Google Scholar 

  47. Brand MI, Casillas S, Dietz DW et al (1996) Development of a reliable colorectal cancer liver metastasis model. J Surg Res 63:425–432

    Article  PubMed  CAS  Google Scholar 

  48. Ravikumar TS, D’Emilia J, Cocchiaro C et al (1989) Experimental liver metastasis. Implications of clonal proclivity and organ specificity. Arch Surg 124:49–54

    PubMed  CAS  Google Scholar 

  49. Sarraf-Yazdi S, Mi J, Dewhirst MW, Clary BM (2004) Use of in vivo bioluminescence imaging to predict hepatic tumor burden in mice. J Surg Res 120:249–255

    Article  PubMed  Google Scholar 

  50. Senger DR, Wirth DF, Hynes RO (1979) Transformed mammalian cells secrete specific proteins and phosphoproteins. Cell 16:885–893

    Article  PubMed  CAS  Google Scholar 

  51. Brown LF, Papadopoulos-Sergiou A, Berse B et al (1994) Osteopontin expression and distribution in human carcinomas. Am J Pathol 145:610–623

    PubMed  CAS  Google Scholar 

  52. Bellahcene A, Castronovo V (1995) Increased expression of osteonectin and osteopontin, two bone matrix proteins, in human breast cancer. Am J Pathol 146:95–100

    PubMed  CAS  Google Scholar 

  53. Hirota S, Ito A, Nagoshi J et al (1995) Expression of bone matrix protein messenger ribonucleic acids in human breast cancers. Possible involvement of osteopontin in development of calcifying foci. Lab Invest 72:64–69

    PubMed  CAS  Google Scholar 

  54. Singhal H, Bautista DS, Tonkin KS et al (1997) Elevated plasma osteopontin in metastatic breast cancer associated with increased tumor burden and decreased survival. Clin Cancer Res 3:605–611

    PubMed  CAS  Google Scholar 

  55. Tuck AB, O’Malley FP, Singhal H et al (1998) Osteopontin expression in a group of lymph node negative breast cancer patients. Int J Cancer 79:502–508

    Article  PubMed  CAS  Google Scholar 

  56. Casson AG, Wilson SM, McCart JA et al (1997) Ras mutation and expression of the ras-regulated genes osteopontin and cathepsin L in human esophageal cancer. Int J Cancer 72:739–745

    Article  PubMed  CAS  Google Scholar 

  57. Gotoh M, Sakamoto M, Kanetaka K et al (2002) Overexpression of osteopontin in hepatocellular carcinoma. Pathol Int 52:19–24

    Article  PubMed  CAS  Google Scholar 

  58. Lin YH, Yang-Yen HF (2001) The osteopontin-CD44 survival signal involves activation of the phosphatidylinositol 3-kinase/Akt signaling pathway. J Biol Chem 276:46024–46030

    Article  PubMed  CAS  Google Scholar 

  59. Hruska KA, Rolnick F, Huskey M et al (1995) Engagement of the osteoclast integrin alpha v beta 3 by osteopontin stimulates phosphatidylinositol 3-hydroxyl kinase activity. Endocrinology 136:2984–2992

    Article  PubMed  CAS  Google Scholar 

  60. Aznavoorian S, Murphy AN, Stetler-Stevenson WG, Liotta LA. (1993) Molecular aspects of tumor cell invasion and metastasis. Cancer 71:1368–1383

    Article  PubMed  CAS  Google Scholar 

  61. Murphy G, Gavrilovic J (1999) Proteolysis and cell migration: creating a path? Curr Opin Cell Biol 11:614–621

    Article  PubMed  CAS  Google Scholar 

  62. Philip S, Bulbule A, Kundu GC (2001) Osteopontin stimulates tumor growth and activation of promatrix metalloproteinase-2 through nuclear factor-kappa B-mediated induction of membrane type 1 matrix metalloproteinase in murine melanoma cells. J Biol Chem 276:44926–44935

    Article  PubMed  CAS  Google Scholar 

  63. Tuck AB, Arsenault DM, O’Malley FP et al (1999) Osteopontin induces increased invasiveness and plasminogen activator expression of human mammary epithelial cells. Oncogene 18:4237–4246

    Article  PubMed  CAS  Google Scholar 

  64. Das R, Mahabeleshwar GH, Kundu GC (2003) Osteopontin stimulates cell motility and nuclear factor kappaB-mediated secretion of urokinase type plasminogen activator through phosphatidylinositol 3-kinase/Akt signaling pathways in breast cancer cells. J Biol Chem 278:28593–28606

    Article  PubMed  CAS  Google Scholar 

  65. Philip S, Kundu GC (2003) Osteopontin induces nuclear factor kappa B-mediated promatrix metalloproteinase-2 activation through I kappa B alpha /IKK signaling pathways, and curcumin (diferulolylmethane) down-regulates these pathways. J Biol Chem 278:14487–14497

    Article  PubMed  CAS  Google Scholar 

  66. Jain S, Chakraborty G, Kundu GC (2006) The crucial role of cyclooxygenase-2 in osteopontin-induced protein kinase C alpha/c-Src/IkappaB kinase alpha/beta-dependent prostate tumor progression and angiogenesis. Cancer Res 66:6638–6648

    Article  PubMed  CAS  Google Scholar 

  67. Rangaswami H, Bulbule A, Kundu GC (2004) Nuclear factor-inducing kinase plays a crucial role in osteopontin-induced MAPK/IkappaBalpha kinase-dependent nuclear factor kappaB-mediated promatrix metalloproteinase-9 activation. J Biol Chem 279:38921–38935

    Article  PubMed  CAS  Google Scholar 

  68. Mi Z, Guo H, Wai PY et al (2006) Integrin-linked kinase regulates osteopontin-dependent MMP-2 and uPA expression to convey metastatic function in murine mammary epithelial cancer cells. Carcinogenesis 27:1134–1145

    Article  PubMed  CAS  Google Scholar 

  69. Wai PY, Mi Z, Guo H et al (2005) Osteopontin silencing by small interfering RNA suppresses in vitro and in vivo CT26 murine colon adenocarcinoma metastasis. Carcinogenesis 26:741–751

    Article  PubMed  CAS  Google Scholar 

  70. Wai PY, Mi Z, Gao C et al (2006) Ets-1 and runx2 regulate transcription of a metastatic gene, osteopontin, in murine colorectal cancer cells. J Biol Chem 281:18973–18982

    Article  PubMed  CAS  Google Scholar 

  71. Friedl P, Wolf K (2003) Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer 3:362–374

    Article  PubMed  CAS  Google Scholar 

  72. Tuck AB, Elliott BE, Hota C et al (2000) Osteopontin-induced, integrin-dependent migration of human mammary epithelial cells involves activation of the hepatocyte growth factor receptor (Met). J Cell Biochem 78:465–475

    Article  PubMed  CAS  Google Scholar 

  73. Tuck AB, Hota C, Wilson SM, Chambers AF (2003) Osteopontin-induced migration of human mammary epithelial cells involves activation of EGF receptor and multiple signal transduction pathways. Oncogene 22:1198–1205

    Article  PubMed  CAS  Google Scholar 

  74. Hayashi C, Rittling S, Hayata T et al (2007) Serum osteopontin, an enhancer of tumor metastasis to bone, promotes B16 melanoma cell migration. J Cell Biochem 101:979–986

    Article  PubMed  CAS  Google Scholar 

  75. Feng B, Rollo EE, Denhardt DT (1995) Osteopontin (OPN) may facilitate metastasis by protecting cells from macrophage NO-mediated cytotoxicity: evidence from cell lines down-regulated for OPN expression by a targeted ribozyme. Clin Exp Metastasis 13:453–462

    Article  PubMed  CAS  Google Scholar 

  76. Denhardt DT, Chambers AF (1994) Overcoming obstacles to metastasis-defenses against host defenses: osteopontin (OPN) as a shield against attack by cytotoxic host cells. J Cell Biochem 56:48–51

    Article  PubMed  CAS  Google Scholar 

  77. Gao C, Guo H, Wei J, Kuo PC (2003) Osteopontin inhibits expression of cytochrome c oxidase in RAW 264.7 murine macrophages. Biochem Biophys Res Commun 309:120–125

    Article  PubMed  CAS  Google Scholar 

  78. Rollo EE, Laskin DL, Denhardt DT (1996) Osteopontin inhibits nitric oxide production and cytotoxicity by activated RAW264.7 macrophages. J Leukoc Biol 60:397–404

    PubMed  CAS  Google Scholar 

  79. Hwang SM, Lopez CA, Heck DE et al (1994) Osteopontin inhibits induction of nitric oxide synthase gene expression by inflammatory mediators in mouse kidney epithelial cells. J Biol Chem 269:711–715

    PubMed  CAS  Google Scholar 

  80. Guo H, Cai CQ, Schroeder RA, Kuo PC (2001) Osteopontin is a negative feedback regulator of nitric oxide synthesis in murine macrophages. J Immunol 166:1079–1086

    PubMed  CAS  Google Scholar 

  81. Nagasaki T, Ishimura E, Koyama H et al (1999) Alphav integrin regulates TNF-alpha-induced nitric oxide synthesis in rat mesangial cells-possible role of osteopontin. Nephrol Dial Transplant 14:1861–1866

    Article  PubMed  CAS  Google Scholar 

  82. Gao C, Guo H, Wei J et al (2004) S-nitrosylation of heterogeneous nuclear ribonucleoprotein A/B regulates osteopontin transcription in endotoxin-stimulated murine macrophages. J Biol Chem 279:11236–11243

    Article  PubMed  CAS  Google Scholar 

  83. Wai PY, Guo L, Gao C et al (2006) Osteopontin inhibits macrophage nitric oxide synthesis to enhance tumor proliferation. Surgery 140:132–140

    Article  PubMed  Google Scholar 

  84. Folkman J (2002) Role of angiogenesis in tumor growth and metastasis. Semin Oncol 29[6 Suppl 16]:15–18

    PubMed  CAS  Google Scholar 

  85. Hanrahan V, Currie MJ, Gunningham SP et al (2003) The angiogenic switch for vascular endothelial growth factor (VEGF)-A, VEGF-B, VEGF-C, and VEGF-D in the adenoma-carcinoma sequence during colorectal cancer progression. J Pathol 200:183–194

    Article  PubMed  CAS  Google Scholar 

  86. Nakamura Y, Yasuoka H, Tsujimoto M et al (2003) Prognostic significance of vascular endothelial growth factor D in breast carcinoma with long-term follow-up. Clin Cancer Res 9: 716–721

    PubMed  CAS  Google Scholar 

  87. Senger DR, Ledbetter SR, Claffey KP et al (1996) Stimulation of endothelial cell migration by vascular permeability factor/vascular endothelial growth factor through cooperative mechanisms involving the alphavbeta3 integrin, osteopontin, and thrombin. Am J Pathol 149:293–305

    PubMed  CAS  Google Scholar 

  88. Scatena M, Almeida M, Chaisson ML et al (1998) NF-kappaB mediates alphavbeta3 integrin-induced endothelial cell survival. J Cell Biol 141:1083–1093

    Article  PubMed  CAS  Google Scholar 

  89. Brooks PC, Montgomery AM, Rosenfeld M et al (1994) Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell 79:1157–1164

    Article  PubMed  CAS  Google Scholar 

  90. Arap W, Pasqualini R, Ruoslahti E (1998) Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science 279:377–380

    Article  PubMed  CAS  Google Scholar 

  91. Bayless KJ, Salazar R, Davis GE (2000) RGD-dependent vacuolation and lumen formation observed during endothelial cell morphogenesis in three-dimensional fibrin matrices involves the alpha(v)beta(3) and alpha(5)beta(1) integrins. Am J Pathol 156: 1673–1683

    PubMed  CAS  Google Scholar 

  92. Hirama M, Takahashi F, Takahashi K et al (2003) Osteopontin overproduced by tumor cells acts as a potent angiogenic factor contributing to tumor growth. Cancer Lett 198:107–117

    Article  PubMed  CAS  Google Scholar 

  93. Leali D, Dell’Era P, Stabile H et al (2003) Osteopontin (Eta-1) and fibroblast growth factor-2 cross-talk in angiogenesis. J Immunol 171:1085–1093

    PubMed  CAS  Google Scholar 

  94. Khan SA, Lopez-Chua CA, Zhang J et al (2002) Soluble osteopontin inhibits apoptosis of adherent endothelial cells deprived of growth factors. J Cell Biochem 85:728–736

    Article  PubMed  CAS  Google Scholar 

  95. Rohde F, Rimkus C, Friederichs J et al (2007) Expression of osteopontin, a target gene of de-regulated Wnt signaling, predicts survival in colon cancer. Int J Cancer 121:1717–1723

    Article  PubMed  CAS  Google Scholar 

  96. Friederichs J, Rosenberg R, Mages J et al (2005) Gene expression profiles of different clinical stages of colorectal carcinoma: toward a molecular genetic understanding of tumor progression. Int J Colorectal Dis 20:391–402

    Article  PubMed  Google Scholar 

  97. Shao J, Washington MK, Saxena R, Sheng H (2007) Heterozygous disruption of the PTEN promotes intestinal neoplasia in APCmin/+ mouse: roles of osteopontin. Carcinogenesis 28:2476–2483

    Article  PubMed  CAS  Google Scholar 

  98. Jain RK (1997) Delivery of molecular and cellular medicine to solid tumors. Adv Drug Deliv Rev 26:71–90

    Article  PubMed  CAS  Google Scholar 

  99. Esau CC, Monia BP (2007) Therapeutic potential for micro-RNAs. Adv Drug Deliv Rev 59:101–114

    Article  PubMed  CAS  Google Scholar 

  100. Shi B, Sepp-Lorenzino L, Prisco M et al (2007) Micro RNA 145 targets the insulin receptor substrate-1 and inhibits the growth of colon cancer cells. J Biol Chem 282:32582–32590

    Article  PubMed  CAS  Google Scholar 

  101. Tazawa H, Tsuchiya N, Izumiya M, Nakagama H (2007) Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells. Proc Natl Acad Sci U S A 104:15472–15477

    Article  PubMed  CAS  Google Scholar 

  102. Lanza G, Ferracin M, Gafa R et al (2007) mRNA/microRNA gene expression profile in microsatellite unstable colorectal cancer. Mol Cancer 6:54

    Article  PubMed  CAS  Google Scholar 

  103. Ireson CR, Kelland LR (2006) Discovery and development of anticancer aptamers. Mol Cancer Ther 5:2957–2962

    Article  PubMed  CAS  Google Scholar 

  104. Lee HK, Choi YS, Park YA, Jeong S (2006) Modulation of oncogenic transcription and alternative splicing by betacatenin and an RNA aptamer in colon cancer cells. Cancer Res 66:10560–10566

    Article  PubMed  CAS  Google Scholar 

  105. Sarraf-Yazdi S, Mi J, Moeller BJ et al (2008) Inhibition of in vivo tumor angiogenesis and growth via systemic delivery of an angiopoietin 2-specific RNA aptamer. J Surg Res 146:16–23

    Article  PubMed  CAS  Google Scholar 

  106. Hijiya N, Setoguchi M, Matsuura K et al (1994) Cloning and characterization of the human osteopontin gene and its promoter. Biochem J 303:255–262

    PubMed  CAS  Google Scholar 

  107. Wai PY, Kuo PC (2004) The role of osteopontin in tumor metastasis. J Surg Res 121:228–241

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Paul C. Kuo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wai, P.Y., Reddy, S.K. & Kuo, P.C. Functional analysis of tumor metastasis: modeling colon cancer. Oncol Rev 2, 9–20 (2008). https://doi.org/10.1007/s12156-008-0051-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12156-008-0051-7

Keywords

Navigation