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The role of the insulin-like growth factor system in colorectal cancer: review of current knowledge

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Abstract

Background

The insulin-like growth factor system, which includes insulin-like growth factors (IGF-I and IGF-II), IGF receptors (IGF-IR and IGF-IIR) and IGF binding proteins (IGFBPs), plays an important role in epithelial growth, anti-apoptosis and mitogenesis. There is a growing body of evidence showing that IGFs control growth and proliferation of several types of cancer. This review introduces the latest information on the biology of the IGF system and its pathophysiological role in the development of colorectal cancer.

Discussion

The growth promoting effects of IGF-I and IGF-II on cancer cells are mediated through the IGF-IR, which is a tyrosine kinase and cancer cells with a strong tendency to metastasise have a higher expression of the IGF-IR. Most of the IGFs in circulation are bound to the IGFBPs, which regulate the bioavailability of the IGFs. All IGFBPs inhibit IGF action by high affinity binding, while some of them also potentiate the effects of IGFs. Colon cancer cells produce specific proteases that degrade the IGFBP so that the IGF will be free to act on the cancer cell in an autocrine manner. Therefore, the IGFBPs play a crucial role in the development of the cancer.

Conclusion

The current knowledge about the link between IGFs and colon cancer is mainly based on in vitro investigations. Further in vivo study is needed to understand the exact role of the IGF system, especially its binding proteins, so that they can be manipulated for the prevention and treatment of colorectal cancer.

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References

  1. Singh P, Dai B, Dhruva B, Widen SG (1994) Episomal expression of sense and antisense insulin-like growth factor (IGF)-binding protein-4 complementary DNA alters the mitogenic response of a human colon cancer cell line (HT-29) by mechanisms that are independent of and dependent upon IGF-I. Cancer Res 54:6563–6570

    Google Scholar 

  2. Kim EJ, Schaffer BS, Kang YH, MacDonald RG, Park JH (2002) Decreased production of insulin-like growth factor-binding protein (IGFBP)-6 by transfection of colon cancer cells with an antisense IGFBP-6 cDNA construct leads to stimulation of cell proliferation. J Gastroenterol Hepatol 17:563–570

    Article  Google Scholar 

  3. Midgley R, Kerr D (1999) Colorectal cancer. Lancet 353:391–399

    Article  CAS  PubMed  Google Scholar 

  4. Boyle P, Langman JS (2000) ABC of colorectal cancer: epidemiology. BMJ 321:805–808

    Article  Google Scholar 

  5. Szepeshazi K, Schally AV, Groot K, Armatis P, Halmos G, Herbert F, Szende B, Varga JL, Zarandi M (2000) Antagonists of growth hormone-releasing hormone (GH-RH) inhibit IGF-II production and growth of HT-29 human colon cancers. Br J Cancer 82:1724–1731

    Article  Google Scholar 

  6. Pollak M (2000) Insulin-like growth factor physiology and cancer risk. Eur J Cancer 36:1224–1228

    Article  Google Scholar 

  7. Grimberg A, Cohen P (2000) Role of Insulin-like growth factors and their binding proteins in growth control and carcinogenesis. J Cell Physiol 183:1–9

    Google Scholar 

  8. Hallberg LM, Ikeno Y, Englander E, George H (2000) Effects of aging and caloric restriction on IGF-I, IGF-I receptor, IGFBP-3 and IGFBP-4 gene expression in the rat stomach and colon. Regul Pept 89:37–44

    Article  Google Scholar 

  9. Leng SL, Leeding KS, Whitehead RH, Bach LA (2001) Insulin-like growth factor (IGF)-binding protein-6 inhibits IGF-II-induced but not basal proliferation and adhesion of LIM 1215 colon cancer cells. Mol Cell Endocrinol 174:121–127

    Article  Google Scholar 

  10. Moschos SJ, Mantzoros CS (2002) The role of the IGF system in cancer: from basic to clinical studies and clinical applications. Oncology 63:317–332

    Google Scholar 

  11. Zhou R, Diehl D, Hoeflich A, Lahm H, Wolf E (2003) IGF-binding protein-4: biochemical characteristics and functional consequences. J Endocrinol 178:177–193

    CAS  PubMed  Google Scholar 

  12. Yu H, Rohan T (2000) Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst 92:1472–1489

    Article  Google Scholar 

  13. Khandwala HM, McCutcheon IE, Flyvbjerg A, Friend KE (2000) The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocr Rev 21:215–244

    Article  Google Scholar 

  14. Giovannucci E (2001) Insulin, insulin-like growth factors and colon cancer: a review of the evidence. J Nutr 131:3109S–3120S

    CAS  PubMed  Google Scholar 

  15. Reinmuth N, Liu W, Fan F, Jung YD, Ahmad SA, Stoeltzing O, Bucana CD, Radinsky R, Ellis LM (2002) Blockade of insulin-like growth factor I receptor function inhibits growth and angiogenesis of colon cancer. Clin Cancer Res 8:3259–3269

    Google Scholar 

  16. Blakesley VA, Scrimgeour A, Esposito D, LeRoith D (1996) Signaling via the insulin-like growth factor-I receptor: does it differ from insulin receptor signaling? Cytokine Growth Factor Rev 7:153–159

    Article  Google Scholar 

  17. LeRoith D, Roberts J (2003) The insulin-like growth factor system and cancer. Cancer Lett 195:127–137

    Google Scholar 

  18. Kim HS, Nagalla SR, Oh Y, Wilson E, Roberts CT Jr, Rosenfeld RG (1997) Identification of a family of low-affinity insulin-like growth factor binding proteins (IGFBPs): characterization of connective tissue growth factor as a member of the IGFBP superfamily. Proc Natl Acad Sci USA 94:12981–12986

    Article  Google Scholar 

  19. Kostecka Y, Blahovec J (1999) Insulin-like growth factor binding proteins and their functions (minireview). Endocr Regul 33:90–94

    Google Scholar 

  20. Baxter RC, Binoux MA, Clemmons DR, Conover CA, Drop SLS, Holly JMP, Mohan S, Oh Y, Rosenfeld RG (1998) Recommendations for nomenclature of the insulin-like growth factor binding protein superfamily. J Clin Endocrinol Metab 83:3213

    Article  Google Scholar 

  21. Mazerbourg S, Callebaut I, Zapf J, Mohan S, Overgaard M, Monget P (2004) Update on IGFBP-4: regulation of IGFBP-4 levels and functions, in vitro and in vivo. Growth Horm IGF Res 14:71–84

    Article  Google Scholar 

  22. Baxter RC (2000) Insulin-like growth factor (IGF)-binding proteins: interactions with IGFs and intrinsic bioactivities. Am J Physiol Endocrinol Metab 278:E967–E976

    CAS  PubMed  Google Scholar 

  23. Zazzi H, Nikoshkov A, Hall K, Luthman H (1998) Structure and transcription regulation of the human insulin-like growth factor binding protein 4 gene (IGFBP4). Genomics 49:401–410

    Article  Google Scholar 

  24. Sandhu MS, Dunger DB, Giovannucci EL (2002) Insulin, insulin-like growth factor-I (IGF-I), IGF binding proteins, their biologic interactions, and colorectal cancer. J Natl Cancer Inst 94:972–980

    Google Scholar 

  25. Remacle-Bonnet MM, Garrouste FL, Pommier GJ (1997) Surface-bound plasmin induces selective proteolysis of insulin-like-growth-factor (IGF)-binding protein-4 (IGFBP-4) and promotes autocrine IGF-II bio-availability in human colon-carcinoma cells. Int J Cancer 72:835–843

    Article  Google Scholar 

  26. Baciuchka M, Remacle-Bonnet M, Garrouste F, Favre R, Sastre B, Pommier G (1998) Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) proteolysis in patients with colorectal cancer: possible association with the metastatic potential of the tumor. Int J Cancer 79:460–467

    Google Scholar 

  27. Kuemmerle JF, Teng B (2000) Regulation of IGFBP-4 levels in human intestinal muscle by an IGF-I-activated, confluence-dependent protease. Am J Physiol Gastrointest Liver Physiol 279:G975–G982

    Google Scholar 

  28. Palmqvist R, Stattin P, Rinaldi S, Biessy C, Stenling R, Riboli E, Hallmans G, Kaaks R (2003) Plasma insulin, IGF-binding proteins-1 and -2 and risk of colorectal cancer: a prospective study in northern Sweden. Int J Cancer 107:89–93

    Article  Google Scholar 

  29. Kaaks R, Toniolo P, Akhmedkhanov A, Lukanova A, Biessy C, Dechaud H, Rinaldi S, Zeleniuch-Jacquotte A, Shore RE, Riboli E (2000) Serum C-peptide, insulin-like growth factor (IGF)-I, IGF-binding proteins, and colorectal cancer risk in women. J Natl Cancer Inst 92:1592–1600

    Article  Google Scholar 

  30. Nomura AM, Stemmermann GN, Lee J, Pollak MN (2003) Serum insulin-like growth factor I and subsequent risk of colorectal cancer among Japanese-American men. Am J Epidemiol 158:424–431

    Article  Google Scholar 

  31. Teramukai S, Rohan T, Lee KY, Eguchi H, Oda T, Kono S (2002) Insulin-like growth factor (IGF)-I, IGF-binding protein-3 and colorectal adenomas in Japanese men. Jpn J Cancer Res 93:1187–1194

    Google Scholar 

  32. Renehan AG, Zwahlen M, Minder C, O’Dwyer ST, Shalet SM, Egger M (2004) Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet 363:1346–1353

    Article  Google Scholar 

  33. Renehan AG, Jones J, O’Dwyer ST, Shalet SM (2003) Determination of IGF-I, IGF-II, IGFBP-2, and IGFBP-3 levels in serum and plasma: comparisons using the Bland-Altman method. Growth Horm IGF Res 13:341–346

    Article  Google Scholar 

  34. Rosenfeld RG (2003) Insulin-like growth factors and the basis of growth. N Engl J Med 349:2184–2186

    Article  Google Scholar 

  35. Reinmuth N, Fan F, Liu W, Parikh AA, Stoeltzing O, Jung YD, Bucana CD, Radinsky R, Gallick GE, Ellis LM (2002) Impact of insulin-like growth factor receptor-I function on angiogenesis, growth, and metastasis of colon cancer. Lab Invest 82:1377–1389

    Google Scholar 

  36. Wu Y, Yakar S, Zhao L, Hennighausen L, LeRoith D (2002) Circulating insulin-like growth factor-I levels regulate colon cancer growth and metastasis. Cancer Res 62:1030–1035

    Google Scholar 

  37. Akagi Y, Liu W, Zebrowski B, Xie K, Ellis LM (1998) Regulation of vascular endothelial growth factor expression in human colon cancer by insulin-like growth factor-I. Cancer Res 58:4008–4014

    Google Scholar 

  38. Fukuda R, Hirota K, Fan F, Jung YD, Ellis LM, Semenza GL (2002) Insulin-like growth factor 1 induces hypoxia-inducible factor 1-mediated vascular endothelial growth factor expression, which is dependent on MAP kinase and phosphatidylinositol 3-kinase signaling in colon cancer cells. J Biol Chem 277:38205–38211

    Article  Google Scholar 

  39. Collard TJ, Guy M, Butt AJ, Perks CM, Holly JMP, Paraskeva C, Williams AC (2003) Transcriptional upregulation of the insulin-like growth factor binding protein IGFBP-3 by sodium butyrate increases IGF-independent apoptosis in human colonic adenoma-derived epithelial cells. Carcinogenesis 24:393–401

    Article  Google Scholar 

  40. Freier S, Weiss O, Eran M, Flyvbjerg A, Dahan R, Nephesh I, Safra T, Shiloni E, Raz I (1999) Expression of the insulin-like growth factors and their receptors in adenocarcinoma of the colon. Gut 44:704–708

    CAS  PubMed  Google Scholar 

  41. Ewton DZ, Kansra S, Lim S, Friedman E (2002) Insulin-like growth factor-I has a biphasic effect on colon carcinoma cells through transient inactivation of forkhead1, initially mitogenic, then mediating growth arrest and differentiation. Int J Cancer 98:665–673

    Article  Google Scholar 

  42. Smith GD, Gunnell D, Holly J (2000) Cancer and insulin-like growth factor-I. A potential mechanism linking the environment with cancer risk. BMJ 321:847–848

    Article  Google Scholar 

  43. Zarrilli R, Pignata S, Romano M, Gravina A, Casola S, Bruni CB, Acquaviva AM (1994) Expression of insulin-like growth factor (IGF)-II and IGF-I receptor during proliferation and differentiation of CaCo-2 human colon carcinoma cells. Cell Growth Differ 5:1085–1091

    Google Scholar 

  44. Hassan AB, Macaulay VM (2002) The insulin-like growth factor system as a therapeutic target in colorectal cancer. Ann Oncol 13:349–356

    Article  Google Scholar 

  45. Manousos O, Souglakos J, Bosetti C, Tzonou A, Chatzidakis V, Trichopoulos D, Adami HO, Mantzoros C (1999) IGF-I and IGF-II in relation to colorectal cancer. Int J Cancer 83:15–17

    Article  CAS  PubMed  Google Scholar 

  46. Howarth GS (2003) Insulin-like growth factor-I and the gastrointestinal system: therapeutic indications and safety implications. J Nutr 133:2109–2112

    Google Scholar 

  47. Ouban A, Muraca P, Yeatman T, Coppola D (2003) Expression and distribution of insulin-like growth factor-1 receptor in human carcinomas. Human Pathol 34:803–808

    Article  Google Scholar 

  48. Hakam A, Yeatman TJ, Lu L, Mora L, Marcet G, Nicosia SV, Karl RC, Coppola D (1999) Expression of insulin-like growth factor-1 receptor in human colorectal cancer. Human Pathol 30:1128–1133

    Article  Google Scholar 

  49. Adenis A, Peyrat JP, Hecquet B, Delobelle A, Depadt G, Quandalle P, Bonneterre J, Demaille A (1995) Type I insulin-like growth factor receptors in human colorectal cancer. Eur J Cancer 31A:50–55

    Article  Google Scholar 

  50. Wang D, Patil S, Li W, Humphrey LE, Brattain MG, Howell GM (2002) Activation of the TGFalpha autocrine loop is downstream of IGF-I receptor activation during mitogenesis in growth factor dependent human colon carcinoma cells. Oncogene 21:2785–2796

    Article  CAS  PubMed  Google Scholar 

  51. Garrouste F, Remacle-Bonnet M, Culouscou JM, Marvaldi J, Pommier G (1991) Type-II insulin-like growth-factor receptor in conditioned medium from HT-29 human colon carcinoma cell line. Int J Cancer 47:760–764

    Google Scholar 

  52. Guo YS, Jin GF, Townsend CM Jr, Zhang T, Sheng HM, Beauchamp RD, Thompson JC (1995) Insulin-like growth factor-II expression in carcinoma in colon cell lines: implications for autocrine actions. J Am Coll Surg 181:145–154

    Google Scholar 

  53. Leng SL, Leeding KS, Gibson PR, Bach LA (2001) Insulin-like growth factor-II renders LIM 2405 human colon cancer cells resistant to butyrate-induced apoptosis: a potential mechanism for colon cancer cell survival in vivo. Carcinogenesis 22:1625–1631

    Article  Google Scholar 

  54. Weber MM, Fottner C, Liu SB, Jung MC, Engelhardt D, Baretton GB (2002) Overexpression of the insulin-like growth factor I receptor in human colon carcinomas. Cancer 95:2086–2095

    Article  Google Scholar 

  55. Feldser D, Agani F, Iyer NV, Pak B, Ferreira G, Semenza GL (1999) Reciprocal positive regulation of hypoxia-inducible factor 1alpha and insulin-like growth factor 2. Cancer Res 59:3915–3918

    Google Scholar 

  56. Michell NP, Langman MJ, Eggo MC (1997) Insulin-like growth factors and their binding proteins in human colonocytes: preferential degradation of insulin-like growth factor binding protein 2 in colonic cancers. Br J Cancer 76:60–66

    CAS  PubMed  Google Scholar 

  57. Jirtle RL (2004) IGF2 loss of imprinting: a potential heritable risk factor for colorectal cancer. Gastroenterology 126:1190–1193

    Article  Google Scholar 

  58. Brenton JD, Viville S, Surani MA (1995) Genomic imprinting and cancer. Cancer Surv 25:161–171

    Google Scholar 

  59. Hu JF, Vu TH, Hoffman AR (1996) Promoter-specific modulation of insulin-like growth factor II genomic imprinting by inhibitors of DNA methylation. J Biol Chem 271:18253–18262

    Article  Google Scholar 

  60. Haig D, Graham C (1991) Genomic imprinting and the strange case of the insulin-like growth factor II receptor. Cell 64:1045–1046

    Article  Google Scholar 

  61. Cruz-Correa M, Cui H, Giardiello FM, Powe NR, Hylind L, Robinson A, Hutcheon DF, Kafonek DR, Brandenburg S, Wu Y, He X, Feinberg AP (2004) Loss of imprinting of insulin growth factor II gene: a potential heritable biomarker for colon neoplasia predisposition. Gastroenterology 126:964–970

    Article  Google Scholar 

  62. Nakagawa H, Chadwick RB, Peltomaki P, Plass C, Nakamura Y, de La Chapelle A (2001) Loss of imprinting of the insulin-like growth factor II gene occurs by biallelic methylation in a core region of H19-associated CTCF-binding sites in colorectal cancer. Proc Natl Acad Sci USA 98:591–596

    Article  Google Scholar 

  63. Cui H, Onyango P, Brandenburg S, Wu Y, Hsieh CL, Feinberg AP (2002) Loss of imprinting in colorectal cancer linked to hypomethylation of H19 and IGF2. Cancer Res 62:6442–6446

    Google Scholar 

  64. Cui H, Cruz-Correa M, Giardiello FM, Hutcheon DF, Kafonek DR, Brandenburg S, Wu Y, He X, Powe NR, Feinberg AP (2003) Loss of IGF2 imprinting: a potential marker of colorectal cancer risk. Science 299:1753–1755

    Article  Google Scholar 

  65. Ma J, Giovannucci E, Pollak M, Chan JM, Gaziano JM, Willett W, Stampfer MJ (2001) Milk intake, circulating levels of insulin-like growth factor-I, and risk of colorectal cancer in men. J Natl Cancer Inst 93:1330–1336

    Article  Google Scholar 

  66. Allen NE, Appleby PN, Davey GK, Kaaks R, Rinaldi S, Key TJ (2002) The associations of diet with serum insulin-like growth factor I and its main binding proteins in 292 women meat-eaters, vegetarians, and vegans. Cancer Epidemiol Biomarkers Prev 11:1441–1448

    Google Scholar 

  67. Norat T, Riboli E (2003) Dairy products and colorectal cancer. A review of possible mechanisms and epidemiological evidence. Eur J Clin Nutr 57:1–17

    Article  CAS  PubMed  Google Scholar 

  68. Yasumaru M, Tsuji S, Tsujii M, Irie T, Komori M, Kimura A, Nishida T, Kakiuchi Y, Kawai N, Murata H, Horimoto M, Sasaki Y, Hayashi N, Kawano S, Hori M (2003) Inhibition of angiotensin II activity enhanced the antitumor effect of cyclooxygenase-2 inhibitors via insulin-like growth factor I receptor pathway. Cancer Res 63:6726–6734

    Google Scholar 

  69. Di Popolo A, Memoli A, Apicella A, Tuccillo C, di Palma A, Ricchi P, Acquaviva AM, Zarrilli R (2000) IGF-II/IGF-I receptor pathway up-regulates COX-2 mRNA expression and PGE2 synthesis in Caco-2 human colon carcinoma cells. Oncogene 19:5517–5524

    Article  Google Scholar 

  70. Hoflich A, Lahm H, Blum W, Kolb H, Wolf E (1998) Insulin-like growth factor-binding protein-2 inhibits proliferation of human embryonic kidney fibroblasts and of IGF-responsive colon carcinoma cell lines. FEBS Lett 434:329–334

    Article  Google Scholar 

  71. Pommier GJ, Garrouste FL, el Atiq F, Roccabianca M, Marvaldi JL, Remacle-Bonnet MM (1992) Potential autocrine role of insulin-like growth factor II during suramin-induced differentiation of HT29-D4 human colonic adenocarcinoma cell line. Cancer Res 52:3182–3188

    Google Scholar 

  72. Nishimura A, Fujimoto M, Oguchi S, Fusunyan RD, MacDermott RP, Sanderson IR (1998) Short-chain fatty acids regulate IGF-binding protein secretion by intestinal epithelial cells. Am J Physiol 275:E55–E63

    Google Scholar 

  73. Kelly RG, Nally K, Shanahan F, O’Connell J (2002) Type I insulin-like growth factor receptor expression on colorectal adenocarcinoma cell lines is decreased in response to the chemopreventive agent N-acetyl-l-cysteine. Ann NY Acad Sci 973:555–558

    Google Scholar 

  74. Kim EJ, Kang IJ, Cho HJ, Kim WK, Ha YL, Park JHY (2003) Conjugated linoleic acid downregulates insulin-like growth factor-I receptor levels in HT-29 human colon cancer cells. J Nutr 133:2675–2681

    Google Scholar 

  75. Perer ES, Madan AK, Shurin A, Zakris E, Romeguera K, Pang Y, Beech DJ (2000) Insulin-like growth factor I receptor antagonism augments response to chemoradiation therapy in colon cancer cells. J Surg Res 94:1–5

    Article  Google Scholar 

  76. Meyerhardt JA, Catalano PJ, Haller DG, Mayer RJ, Macdonald JS, Benson AB III, Fuchs CS (2003) Impact of diabetes mellitus on outcomes in patients with colon cancer. J Clin Oncol 21:433–440

    Article  Google Scholar 

  77. Miraki-Moud F, Jenkins PJ, Fairclough PD, Jordan S, Bustin SA, Jones AM, Lowe DG, Monson JP, Grossman AB, Besser GM, Camacho-Hubner C (2001) Increased levels of insulin-like growth factor binding protein-2 in sera and tumours from patients with colonic neoplasia with and without acromegaly. Clin Endocrinol (Oxf) 54:499–508

    Article  Google Scholar 

  78. Jenkins PJ, Frajese V, Jones AM, Camacho-Hubner C, Lowe DG, Fairclough PD, Chew SL, Grossman AB, Monson JP, Besser GM (2000) Insulin-like growth factor I and the development of colorectal neoplasia in acromegaly. J Clin Endocrinol Metab 85:3218–3221

    Article  Google Scholar 

  79. Guo YS, Narayan S, Yallampalli C, Singh P (1992) Characterization of insulinlike growth factor I receptors in human colon cancer. Gastroenterology 102:1101–1108

    Google Scholar 

  80. Singh P, Dai B, Yallampalli C, Xu Z (1994) Expression of IGF-II and IGF-binding proteins by colon cancer cells in relation to growth response to IGFs. Am J Physiol 267:G608–G617

    Google Scholar 

  81. Oguchi S, Walker WA, Sanderson IR (1993) Insulin-like growth factor binding protein profile secreted by human intestinal epithelial cells varies with polarity. Biochem Biophys Res Commun 196:789–793

    Article  Google Scholar 

  82. Remacle-Bonnet M, Garrouste F, el Atiq F, Roccabianca M, Marvaldi J, Pommier G (1992) Des-(1–3)-IGF-I, an insulin-like growth factor analog used to mimic a potential IGF-II autocrine loop, promotes the differentiation of human colon-carcinoma cells. Int J Cancer 52:910–917

    Google Scholar 

  83. Mishra L, Bass B, Ooi BS, Sidawy A, Korman L (1998) Role of insulin-like growth factor-I (IGF-I) receptor, IGF-I, and IGF binding protein-2 in human colorectal cancers. Growth Horm IGF Res 8:473–479

    Google Scholar 

  84. Singh P, Dai B, Yallampalli U, Lu X, Schroy PC (1996) Proliferation and differentiation of a human colon cancer cell line (CaCo2) is associated with significant changes in the expression and secretion of insulin-like growth factor (IGF) IGF-II and IGF binding protein-4: role of IGF-II. Endocrinology 137:1764–1774

    Article  Google Scholar 

  85. Zhang Y, Wick DA, Seetharam B, Dahms NM (1995) Expression of IGF-II and IGF binding proteins in differentiating human intestinal Caco-2 cells. Am J Physiol Endocrinol Metab 269:E804–E813

    Google Scholar 

  86. Hunt KJ, Toniolo P, Akhmedkhanov A, Lukanova A, Dechaud H, Rinaldi S, Zeleniuch-Jacquotte A, Shore RE, Riboli E, Kaaks R (2002) Insulin-like growth factor II and colorectal cancer risk in women. Cancer Epidemiol Biomarkers Prev 11:901–905

    Google Scholar 

  87. Firth SM, Baxter RC (2002) Cellular actions of the insulin-like growth factor binding proteins. Endocr Rev 23:824–854

    Article  CAS  PubMed  Google Scholar 

  88. Dai B, Widen SG, Mifflin R, Singh P (1997) Cloning of the functional promoter for human insulin-like growth factor binding protein-4 gene: endogenous regulation. Endocrinology 138:332–343

    Article  Google Scholar 

  89. Hoeflich A, Reisinger R, Lahm H, Kiess W, Blum WF, Kolb HJ, Weber MM, Wolf E (2001) Insulin-like growth factor-binding protein 2 in tumorigenesis: protector or promoter? Cancer Res 61:8601–8610

    Google Scholar 

  90. Reeve JG, Kirby LB, Brinkman A, Hughes SA, Schwander J, Bleehen NM (1992) Insulin-like growth-factor-binding protein gene expression and protein production by human tumour cell lines. Int J Cancer 51:818–821

    Google Scholar 

  91. Michell NP, Dent S, Langman MJ, Eggo MC (1997) Insulin-like growth factor binding proteins as mediators of IGF-I effects on colon cancer cell proliferation. Growth Factors 14:269–277

    Google Scholar 

  92. Renehan AG, Jones J, Potten CS, Shalet SM, O’Dwyer ST (2000) Elevated serum insulin-like growth factor (IGF)-II and IGF binding protein-2 in patients with colorectal cancer. Br J Cancer 83:1344–1350

    Article  Google Scholar 

  93. MacDonald RG, Schaffer BS, Kang IJ, Hong SM, Kim EJ, Park JH (1999) Growth inhibition and differentiation of the human colon carcinoma cell line, Caco-2, by constitutive expression of insulin-like growth factor binding protein-3. J Gastroenterol Hepatol 14:72–78

    Article  Google Scholar 

  94. Kansra S, Ewton DZ, Wang J, Friedman E (2000) IGFBP-3 mediates TGF beta 1 proliferative response in colon cancer cells. Int J Cancer 87:373–378

    Article  Google Scholar 

  95. Williams AC, Collard TJ, Perks CM, Newcomb P, Moorghen M, Holly JM, Paraskeva C (2000) Increased p53-dependent apoptosis by the insulin-like growth factor binding protein IGFBP-3 in human colonic adenoma-derived cells. Cancer Res 60:22–27

    Google Scholar 

  96. Giovannucci E, Pollak MN, Platz EA, Willett WC, Stampfer MJ, Majeed N, Colditz GA, Speizer FE, Hankinson SE (2000) A prospective study of plasma insulin-like growth factor-1 and binding protein-3 and risk of colorectal neoplasia in women. Cancer Epidemiol Biomarkers Prev 9:345–349

    Google Scholar 

  97. Oh Y, Nagalla SR, Yamanaka Y, Kim HS, Wilson E, Rosenfeld RG (1996) Synthesis and characterization of insulin-like growth factor-binding protein (IGFBP)-7. Recombinant human mac25 protein specifically binds IGF-I and -II. J Biol Chem 271:30322–30325

    Article  Google Scholar 

  98. Miyamoto S, Yano K, Sugimoto S, Ishii G, Hasebe T, Endoh Y, Kodama K, Goya M, Chiba T, Ochiai A (2004) Matrix metalloproteinase-7 facilitates insulin-like growth factor bioavailability through its proteinase activity on insulin-like growth factor binding protein 3. Cancer Res 64:665–671

    CAS  PubMed  Google Scholar 

  99. Monitto CL, Berkowitz D, Lee KM, Pin S, Li D, Breslow M, O’Malley B, Schiller M (2001) Differential gene expression in a murine model of cancer cachexia. Am J Physiol Endocrinol Metab 281:E289–E297

    Google Scholar 

  100. Diehl D, Hoeflich A, Wolf E, Lahm H (2004) Insulin-like growth factor (IGF)-binding protein-4 inhibits colony formation of colorectal cancer cells by IGF-independent mechanisms. Cancer Res 64:1600–1603

    CAS  PubMed  Google Scholar 

  101. Butt AJ, Dickson KA, McDougall F, Baxter RC (2003) Insulin-like growth factor-binding protein-5 inhibits the growth of human breast cancer cells in vitro and in vivo. J Biol Chem 278:29676–29685

    Article  Google Scholar 

  102. Schneider MR, Wolf E, Hoeflich A, Lahm H (2002) IGF-binding protein 5: flexible player in the IGF system and effector on its own. J Endocrinol 172:423–440

    CAS  PubMed  Google Scholar 

  103. Oh YS, Kim EJ, Schaffer BS, Kang YH, Binderup L, MacDonald RG, Park JH (2001) Synthetic low-calcaemic vitamin D(3) analogues inhibit secretion of insulin-like growth factor II and stimulate production of insulin-like growth factor-binding protein-6 in conjunction with growth suppression of HT-29 colon cancer cells. Mol Cell Endocrinol 183:141–149

    Article  Google Scholar 

  104. Kim EJ, Kim WY, Kang YH, Ha YL, Bach LA, Park JHY (2000) Inhibition of CACO-2 cell proliferation by (n-3) fatty acids: possible mediation by increased secretion of insulin-like growth factor binding protein-6. Nutr Res 20:1409–1421

    Article  Google Scholar 

  105. Shao L, Huang Q, Luo M, Lai M (2003) Detection of the differentially expressed gene IGFBP-rP1 and analysis of its relationship to fasting glucose in Chinese colorectal cancer patients. Endocr Relat Cancer 11:141–148

    Article  Google Scholar 

  106. Rajaram S, Baylink DJ, Mohan S (1997) Insulin-like growth factor-binding proteins in serum and other biological fluids: regulation and functions. Endocr Rev 18:801–831

    Article  CAS  PubMed  Google Scholar 

  107. Degeorges A, Wang F, Frierson HF Jr, Seth A, Sikes RA (2000) Distribution of IGFBP-rP1 in normal human tissues. J Histochem Cytochem 48:747–754

    Google Scholar 

  108. Ma J, Pollak M, Giovannucci E, Chan JM, Tao Y, Hennekens C, Stampfer MJ (2000) A prospective study of plasma levels of insulin-like growth factor I (IGF-I) and IGF-binding protein-3, and colorectal cancer risk among men. Growth Horm IGF Res 10 [Suppl A]:S28–S29

    Article  Google Scholar 

  109. Probst-Hensch NM, Yuan JM, Stanczyk FZ, Gao YT, Ross RK, Yu MC (2001) IGF-1, IGF-2 and IGFBP-3 in prediagnostic serum: association with colorectal cancer in a cohort of Chinese men in Shanghai. Br J Cancer 85:1695–1699

    Article  Google Scholar 

  110. Renehan AG, Painter JE, Atkin WS, Potten CS, Shalet SM, O’Dwyer ST (2001) High-risk colorectal adenomas and serum insulin-like growth factors. Br J Surg 88:107–113

    Article  CAS  PubMed  Google Scholar 

  111. El Atiq F, Garrouste F, Remacle-Bonnet M, Sastre B, Pommier G (1994) Alterations in serum levels of insulin-like growth factors and insulin-like growth-factor-binding proteins in patients with colorectal cancer. Int J Cancer 57:491–497

    Google Scholar 

  112. Renehan AG, Toogood AA, Ryder WD, Jones J, Potten CS, O’Dwyer ST, Shalet SM (2001) Paradoxical elevations in serum IGF-II and IGF binding protein-2 in acromegaly: insights into the regulation of these peptides. Clin Endocrinol (Oxf) 55:469–475

    Article  Google Scholar 

  113. Renehan AG, Painter JE, O’Halloran D, Atkin WS, Potten CS, O’Dwyer ST, Shalet SM (2000) Circulating insulin-like growth factor II and colorectal adenomas. J Clin Endocrinol Metab 85:3402–3408

    Article  CAS  PubMed  Google Scholar 

  114. Culouscou JM, Shoyab M (1991) Purification of a colon cancer cell growth inhibitor and its identification as an insulin-like growth factor binding protein. Cancer Res 51:2813–2819

    Google Scholar 

  115. Saksena M, Miraki-Moud F, King P, Camacho-Hubner C (2002) Effect of insulin-like growth factor binding protein-3 (IGFBP-3) on colon cancer epithelial cells growth and apoptosis [abstract]. Endocr Abstr 4:OC15

    Google Scholar 

  116. David TM, Khalaf S, Davies D, Bustin S, Jenkins PJ (2004) The influence of IGFBP-3 on colonic epithelial cell proliferation and apoptosis [abstract]. Endocr Abstr 2:P22

    Google Scholar 

  117. Kim EJ, Kang YH, Schaffer BS, Bach LA, MacDonald RG, Park JH (2002) Inhibition of Caco-2 cell proliferation by all-trans retinoic acid: role of insulin-like growth factor binding protein-6. J Cell Physiol 190:92–100

    Article  Google Scholar 

  118. Kim EJ, Holthuizen PE, Park HS, Ha YL, Jung KC, Park JH (2002) Trans-10,cis-12-conjugated linoleic acid inhibits Caco-2 colon cancer cell growth. Am J Physiol Gastrointest Liver Physiol 283:G357–G367

    Google Scholar 

  119. Kirman I, Cekic V, Poltaratskaia N, Asi Z, Bessler M, Huang EH, Forde KA, Whelan RL (2002) Plasma from patients undergoing major open surgery stimulates in vitro tumor growth: lower insulin-like growth factor binding protein 3 levels may, in part, account for this change. Surgery 132:186–192

    Article  PubMed  Google Scholar 

  120. Cho HJ, Lee HS, Chung CK, Kang YH, Ha YL, Park HS, Park JH (2003) Trans-10, cis-12 conjugated linoleic acid reduces insulin-like growth factor-II secretion in HT-29 human colon cancer cells. J Med Food 6:193–199

    Article  Google Scholar 

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Authors and Affiliations

  1. University Department of Surgery, Royal Free and University College Medical School, University College London, Rowland Hill Street, London, NW3 2PF, UK

    Rajaraman Durai, Wenxuan Yang, Alexander M. Seifalian & Marc C. Winslet

  2. Royal Free Hampstead NHS Trust Hospital, Pond Street, London, NW3 2QG, UK

    Sharmila Gupta & Marc C. Winslet

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  1. Rajaraman Durai
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  2. Wenxuan Yang
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  3. Sharmila Gupta
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  4. Alexander M. Seifalian
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  5. Marc C. Winslet
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Correspondence to Alexander M. Seifalian.

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Durai, R., Yang, W., Gupta, S. et al. The role of the insulin-like growth factor system in colorectal cancer: review of current knowledge. Int J Colorectal Dis 20, 203–220 (2005). https://doi.org/10.1007/s00384-004-0675-4

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