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Regulation of Breast Cancer Metastasis by IGF Signaling

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

The insulin-like growth factors (IGFs) signaling via the type I insulin-like growth factor receptor (IGF-1R) regulate multiple aspects of malignancy. The importance of IGF-1R in regulating the malignant phenotype is currently being validated in numerous clinical trials for cancer including breast cancer. This review discusses the regulation of breast cancer metastasis by IGF-1R. IGF-1R stimulates invasion and survival in anchorage independent conditions. The regulation of metastasis independently of tumor growth by IGF-1R is also discussed. Finally, the impact of this on clinical trial design and outcomes, and the need for biomarkers, other than reduction in tumor size, are discussed in light of the fact that inhibition of metastasis is not measured in conventional clinical trial design.

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Abbreviations

AI:

aromatase inhibitor

DCE-MRI:

dynamic-contrast enhanced-MRI

ER:

estrogen receptor

IGF:

insulin-like growth factor

IGFBPs:

IGF binding proteins

IGF-1R:

type I IGF receptor

IR:

insulin receptor

IRS:

insulin receptor substrate

MAPK:

mitogen-activated protein kinase

MMTV:

mouse mammary tumor virus

MRS:

magnetic resonance spectroscopy

PI3K:

phosphatidylinositol 3′ kinase

PET:

positron emission tomography

PyV-MT:

polyoma virus middle T antigen

RACK1:

scaffolding protein receptor for activated C kinase

RTK:

receptor tyrosine kinases

SERM:

selective estrogen receptor modulator

SHC:

Src-homology containing protein

WAP:

whey acidic protein

References

  1. Gschwind A, Fischer OM, Ullrich A. The discovery of receptor tyrosine kinases: targets for cancer therapy. Nat Rev Cancer. 2004;4:361–70. doi:10.1038/nrc1360.

    Article  PubMed  CAS  Google Scholar 

  2. Perona R. Cell signalling: growth factors and tyrosine kinase receptors. Clin Transl Oncol. 2006;8:77–82. doi:10.1007/s12094-006-0162-1.

    Article  PubMed  CAS  Google Scholar 

  3. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783–92. doi:10.1056/NEJM200103153441101.

    Article  PubMed  CAS  Google Scholar 

  4. Chambers AF, Groom AC, MacDonald IC. Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer. 2002;2:563–72. doi:10.1038/nrc865.

    Article  PubMed  CAS  Google Scholar 

  5. Gupta GP, Massague J. Cancer metastasis: building a framework. Cell. 2006;127:679–95. doi:10.1016/j.cell.2006.11.001.

    Article  PubMed  CAS  Google Scholar 

  6. Maloney EK, McLaughlin JL, Dagdigian NE, Garrett LM, Connors KM, Zhou XM, et al. An anti-insulin-like growth factor I receptor antibody that is a potent inhibitor of cancer cell proliferation. Cancer Res. 2003;63:5073–83.

    PubMed  CAS  Google Scholar 

  7. Burtrum D, Zhu Z, Lu D, Anderson DM, Prewett M, Pereira DS, et al. A fully human monoclonal antibody to the insulin-like growth factor I receptor blocks ligand-dependent signaling and inhibits human tumor growth in vivo. Cancer Res. 2003;63:8912–21.

    PubMed  CAS  Google Scholar 

  8. Cohen BD, Baker DA, Soderstrom C, Tkalcevic G, Rossi AM, Miller PE, et al. Combination therapy enhances the inhibition of tumor growth with the fully human anti-type 1 insulin-like growth factor receptor monoclonal antibody CP-751,871. Clin Cancer Res. 2005;11:2063–73. doi:10.1158/1078-0432.CCR-04-1070.

    Article  PubMed  CAS  Google Scholar 

  9. Wang Y, Hailey J, Williams D, Lipari P, Malkowski M, Wang X, et al. Inhibition of insulin-like growth factor-I receptor (IGF-IR) signaling and tumor cell growth by a fully human neutralizing anti-IGF-IR antibody. Mol Cancer Ther. 2005;4:1214–21. doi:10.1158/1535-7163.MCT-05-0048.

    Article  PubMed  CAS  Google Scholar 

  10. Goetsch L, Gonzalez A, Leger O, Beck A, Pauwels PJ, Haeuw JF, et al. A recombinant humanized anti-insulin-like growth factor receptor type I antibody (h7C10) enhances the antitumor activity of vinorelbine and anti-epidermal growth factor receptor therapy against human cancer xenografts. Int J Cancer. 2005;113:316–28. doi:10.1002/ijc.20543.

    Article  PubMed  CAS  Google Scholar 

  11. Wittman M, Carboni J, Attar R, Balasubramanian B, Balimane P, Brassil P, et al. Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitumor activity. J Med Chem. 2005;48:5639–43. doi:10.1021/jm050392q.

    Article  PubMed  CAS  Google Scholar 

  12. Haluska P, Carboni JM, Loegering DA, Lee FY, Wittman M, Saulnier MG, et al. In vitro and in vivo antitumor effects of the dual insulin-like growth factor-I/insulin receptor inhibitor, BMS-554417. Cancer Res. 2006;66:362–71. doi:10.1158/0008-5472.CAN-05-1107.

    Article  PubMed  CAS  Google Scholar 

  13. Ji QS, Mulvihill MJ, Rosenfeld-Franklin M, Cooke A, Feng L, Mak G, et al. A novel, potent, and selective insulin-like growth factor-I receptor kinase inhibitor blocks insulin-like growth factor-I receptor signaling in vitro and inhibits insulin-like growth factor-I receptor dependent tumor growth in vivo. Mol Cancer Ther. 2007;6:2158–67. doi:10.1158/1535-7163.MCT-07-0070.

    Article  PubMed  CAS  Google Scholar 

  14. Haluska P, Shaw HM, Batzel GN, Yin D, Molina JR, Molife LR, et al. Phase I dose escalation study of the anti insulin-like growth factor-I receptor monoclonal antibody CP-751,871 in patients with refractory solid tumors. Clin Cancer Res. 2007;13:5834–40. doi:10.1158/1078-0432.CCR-07-1118.

    Article  PubMed  CAS  Google Scholar 

  15. Rowinsky EK, Youssoufian H, Tonra JR, Solomon P, Burtrum D, Ludwig DL. IMC-A12, a human IgG1 monoclonal antibody to the insulin-like growth factor I receptor. Clin Cancer Res. 2007;13:5549s–55s. doi:10.1158/1078-0432.CCR-07-1109.

    Article  PubMed  CAS  Google Scholar 

  16. Tolcher AW, Patnaik A, Till E, Takimoto CH, Papadopoulos KP, Massard C, et al. A phase I study of AVE1642, a humanized monoclonal antibody IGF-1R (insulin like growth factor1 receptor) antagonist, in patients (pts) with advanced solid tumor (ST). J Clin Oncol. 2008;26:3582.

    Article  CAS  Google Scholar 

  17. Rodon J, DeSantos V, Ferry RJ Jr, Kurzrock R. Early drug development of inhibitors of the insulin-like growth factor-I receptor pathway: lessons from the first clinical trials. Mol Cancer Ther. 2008;7:2575–88. doi:10.1158/1535-7163.MCT-08-0265.

    Article  PubMed  CAS  Google Scholar 

  18. Pollak MN. Insulin-like growth factors and neoplasia. Novartis Found Symp. 2004;262:84–98. discussion 98–107.

    Article  PubMed  CAS  Google Scholar 

  19. Baserga R. Targeting the IGF-1 receptor: from rags to riches. Eur J Cancer. 2004;40:2013–5. doi:10.1016/j.ejca.2004.06.015.

    Article  PubMed  Google Scholar 

  20. Bohula EA, Playford MP, Macaulay VM. Targeting the type 1 insulin-like growth factor receptor as anti-cancer treatment. Anticancer Drugs. 2003;14:669–82. doi:10.1097/00001813-200310000-00001.

    Article  PubMed  CAS  Google Scholar 

  21. Clemmons DR. Modifying IGF1 activity: an approach to treat endocrine disorders, atherosclerosis and cancer. Nat Rev Drug Discov. 2007;6:821–33. doi:10.1038/nrd2359.

    Article  PubMed  CAS  Google Scholar 

  22. LeRoith D, Roberts CT Jr. The insulin-like growth factor system and cancer. Cancer Lett. 2003;195:127–37.

    PubMed  CAS  Google Scholar 

  23. Firth SM, Baxter RC. Cellular actions of the insulin-like growth factor binding proteins. Endocr Rev. 2002;23:824–54. doi:10.1210/er.2001-0033.

    Article  PubMed  CAS  Google Scholar 

  24. Ullrich A, Gray A, Tam AW, Yang Feng T, Tsubokawa M, Collins C, et al. Insulin-like growth factor I receptor primary structure:comparison with insulin receptor suggests structural determinants that define hormonal specificity. EMBO J. 1986;5:2503–12.

    PubMed  CAS  Google Scholar 

  25. Tollefsen SE, Stoszek RM, Thompson K. Interaction of the alpha-beta dimers of the insulin-like growth factor I receptor is required for receptor autophosphorylation. Biochemistry. 1991;30:48–54. doi:10.1021/bi00215a008.

    Article  PubMed  CAS  Google Scholar 

  26. Demeyts P, Wallach B, Christoffersen CT, Urso B, Gronskov K, Latus LJ, et al. The insulin-like growth factor-I receptor—structure, ligand-binding mechanism and signal transduction. Horm Res. 1994;42:152–69.

    CAS  Google Scholar 

  27. Frasca F, Pandini G, Scalia P, Sciacca L, Mineo R, Costantino A, et al. Insulin receptor isoform A, a newly recognized, high-affinity insulin-like growth factor II receptor in fetal and cancer cells. Mol Cell Biol. 1999;19:3278–88.

    PubMed  CAS  Google Scholar 

  28. Ludwig T, Eggenschwiler J, Fisher P, D’Ercole AJ, Davenport ML, Efstratiadis A. Mouse mutants lacking the type 2 IGF receptor (IGF2R) are rescued from perinatal lethality in Igf2 and Igf1r null backgrounds. Dev Biol. 1996;177:517–35. doi:10.1006/dbio.1996.0182.

    Article  PubMed  CAS  Google Scholar 

  29. Di Cola G, Cool MH, Accili D. Hypoglycemic effect of insulin-like growth factor-1 in mice lacking insulin receptors. J Clin Invest. 1997;99:2538–44. doi:10.1172/JCI119438.

    Article  PubMed  Google Scholar 

  30. Kim JJ, Accilli D. Signalling through IGF-I and insulin receptors: where is the specificity? Growth Horm IGF Res. 2002;12:84–90; see comment. doi:10.1054/ghir.2002.0265

    Article  PubMed  CAS  Google Scholar 

  31. Pandini G, Vigneri R, Costantino A, Frasca F, Ippolito A, Fujita-Yamaguchi Y, et al. Insulin and insulin-like growth factor-I (IGF-I) receptor overexpression in breast cancers leads to insulin/IGF-I hybrid receptor overexpression: evidence for a second mechanism of IGF-I signaling. Clin Cancer Res. 1999;5:1935–44.

    PubMed  CAS  Google Scholar 

  32. Frasca F, Pandini G, Vigneri R, Goldfine ID. Insulin and hybrid insulin/IGF receptors are major regulators of breast cancer cells. Breast Dis. 2003;17:73–89.

    PubMed  CAS  Google Scholar 

  33. Pandini G, Frasca F, Mineo R, Sciacca L, Vigneri R, Belfiore A. Insulin/insulin-like growth factor I hybrid receptors have different biological characteristics depending on the insulin receptor isoform involved. J Biol Chem. 2002;277:39684–95. doi:10.1074/jbc.M202766200.

    Article  PubMed  CAS  Google Scholar 

  34. Morgan DO, Edman JC, Standring DN, Fried VA, Smith MC, Roth RA, et al. Insulin-like growth factor II receptor as a multifunctional binding protein. Nature. 1987;329:301–7; published erratum appears in Nature 1988 Jul;20(7):442. doi:10.1038/329301a0

    Article  PubMed  CAS  Google Scholar 

  35. Kiess W, Blickenstaff GD, Sklar MM, Thomas CL, Nissley SP, Sahagian GG. Biochemical evidence that the type II insulin-like growth factor receptor is identical to the cation-independent mannose 6-phosphate receptor. J Biol Chem. 1988;263:9339–44.

    PubMed  CAS  Google Scholar 

  36. MacDonald RG, Pfeffer SR, Coussens L, Tepper MA, Brocklebank CM, Mole JE, et al. A single receptor binds both insulin-like growth factor II and mannose-6-phosphate. Science. 1988;239:1134–7. doi:10.1126/science.2964083.

    Article  PubMed  CAS  Google Scholar 

  37. Byrd JC, Devi GR, de Souza AT, Jirtle RL, MacDonald RG. Disruption of ligand binding to the insulin-like growth factor II/mannose 6-phosphate receptor by cancer-associated missense mutations. J Biol Chem. 1999;274:24408–16. doi:10.1074/jbc.274.34.24408.

    Article  PubMed  CAS  Google Scholar 

  38. Jackson JG, White MF, Yee D. Insulin receptor substrate-1 is the predominant signaling molecule activated by insulin-like growth factor-I, insulin, and interleukin-4 in estrogen receptor-positive human breast cancer cells. J Biol Chem. 1998;273:9994–10003. doi:10.1074/jbc.273.16.9994.

    Article  PubMed  CAS  Google Scholar 

  39. Yoneda T, Williams PJ, Hiraga T, Niewolna M, Nishimura R. A bone-seeking clone exhibits different biological properties from the MDA-MB-231 parental human breast cancer cells and a brain-seeking clone in vivo and in vitro. J Bone Miner Res. 2001;16:1486–95. doi:10.1359/jbmr.2001.16.8.1486.

    Article  PubMed  CAS  Google Scholar 

  40. Jackson JG, Zhang X, Yoneda T, Yee D. Regulation of breast cancer cell motility by insulin receptor substrate-2 (IRS-2) in metastatic variants of human breast cancer cell lines. Oncogene. 2001;20:7318–25. doi:10.1038/sj.onc.1204920.

    Article  PubMed  CAS  Google Scholar 

  41. Byron SA, Horwitz KB, Richer JK, Lange CA, Zhang X, Yee D. Insulin receptor substrates mediate distinct biological responses to insulin-like growth factor receptor activation in breast cancer cells. Br J Cancer. 2006;95:1220–8. doi:10.1038/sj.bjc.6603354.

    Article  PubMed  CAS  Google Scholar 

  42. Gibson SL, Ma Z, Shaw LM. Divergent roles for IRS-1 and IRS-2 in breast cancer metastasis. Cell Cycle. 2007;6:631–7.

    PubMed  CAS  Google Scholar 

  43. Nagle JA, Ma Z, Byrne MA, White MF, Shaw LM. Involvement of insulin receptor substrate 2 in mammary tumor metastasis. Mol Cell Biol. 2004;24:9726–35. doi:10.1128/MCB.24.22.9726-9735.2004.

    Article  PubMed  CAS  Google Scholar 

  44. Ma Z, Gibson SL, Byrne MA, Zhang J, White MF, Shaw LM. Suppression of insulin receptor substrate 1 (IRS-1) promotes mammary tumor metastasis. Mol Cell Biol. 2006;26:9338–51. doi:10.1128/MCB.01032-06.

    Article  PubMed  CAS  Google Scholar 

  45. Dearth RK, Cui X, Kim HJ, Kuiatse I, Lawrence NA, Zhang X, et al. Mammary tumorigenesis and metastasis caused by overexpression of insulin receptor substrate 1 (IRS-1) or IRS-2. Mol Cell Biol. 2006;26:9302–14. doi:10.1128/MCB.00260-06.

    Article  PubMed  CAS  Google Scholar 

  46. Zhang X, Kamaraju S, Hakuno F, Kabuta T, Takahashi S, Sachdev D, et al. Motility response to insulin-like growth factor-I (IGF-I) in MCF-7 cells is associated with IRS-2 activation and integrin expression. Breast Cancer Res Treat. 2004;83:161–70. doi:10.1023/B:BREA.0000010709.31256.c6.

    Article  PubMed  CAS  Google Scholar 

  47. Kiely PA, Leahy M, O’Gorman D, O’Connor R. RACK1-mediated integration of adhesion and insulin-like growth factor I (IGF-I) signaling and cell migration are defective in cells expressing an IGF-I receptor mutated at tyrosines 1250 and 1251. J Biol Chem. 2005;280:7624–33. doi:10.1074/jbc.M412889200.

    Article  PubMed  CAS  Google Scholar 

  48. Hermanto U, Zong CS, Li W, Wang LH. RACK1, an insulin-like growth factor I (IGF-I) receptor-interacting protein, modulates IGF-I-dependent integrin signaling and promotes cell spreading and contact with extracellular matrix. Mol Cell Biol. 2002;22:2345–65. doi:10.1128/MCB.22.7.2345-2365.2002.

    Article  PubMed  CAS  Google Scholar 

  49. Kiely PA, O’Gorman D, Luong K, Ron D, O’Connor R. Insulin-like growth factor I controls a mutually exclusive association of RACK1 with protein phosphatase 2A and beta1 integrin to promote cell migration. Mol Cell Biol. 2006;26:4041–51. doi:10.1128/MCB.01868-05.

    Article  PubMed  CAS  Google Scholar 

  50. Kiely PA, Baillie GS, Lynch MJ, Houslay MD, O’Connor R. Tyrosine 302 in RACK1 Is essential for insulin-like growth factor-I-mediated competitive binding of PP2A and beta1 Integrin and for tumor cell proliferation and migration. J Biol Chem. 2008;283:22952–61. doi:10.1074/jbc.M800802200.

    Article  PubMed  CAS  Google Scholar 

  51. Prager D, Li HL, Asa S, Melmed S. Dominant negative inhibition of tumorigenesis in vivo by human insulin-like growth factor I receptor mutant. Proc Natl Acad Sci U S A. 1994;91:2181–5. doi:10.1073/pnas.91.6.2181.

    Article  PubMed  CAS  Google Scholar 

  52. Long L, Rubin R, Baserga R, Brodt P. Loss of the metastatic phenotype in murine carcinoma cells expressing an antisense RNA to the insulin-like growth factor receptor. Cancer Res. 1995;55:1006–9.

    PubMed  CAS  Google Scholar 

  53. Dunn SE, Ehrlich M, Sharp NJ, Reiss K, Solomon G, Hawkins R, et al. A dominant negative mutant of the insulin-like growth factor-I receptor inhibits the adhesion, invasion, and metastasis of breast cancer. Cancer Res. 1998;58:3353–61.

    PubMed  CAS  Google Scholar 

  54. Sachdev D, Hartell JS, Lee AV, Zhang X, Yee D. A dominant negative type I insulin-like growth factor receptor inhibits metastasis of human cancer cells. J Biol Chem. 2004;279:5017–24. doi:10.1074/jbc.M305403200.

    Article  PubMed  CAS  Google Scholar 

  55. Chatzistamou I, Schally AV, Varga JL, Groot K, Busto R, Armatis P, et al. Inhibition of growth and metastases of MDA-MB-435 human estrogen-independent breast cancers by an antagonist of growth hormone-releasing hormone. Anticancer Drugs. 2001;12:761–8. doi:10.1097/00001813-200110000-00008.

    Article  PubMed  CAS  Google Scholar 

  56. Reinmuth N, Fan F, Liu W, Parikh AA, Stoeltzing O, Jung YD, et al. Impact of insulin-like growth factor receptor-I function on angiogenesis, growth, and metastasis of colon cancer. Lab Invest. 2002;82:1377–89.

    PubMed  CAS  Google Scholar 

  57. Wu Y, Yakar S, Zhao L, Hennighausen L, LeRoith D. Circulating insulin-like growth factor-I levels regulate colon cancer growth and metastasis. Cancer Res. 2002;62:1030–5.

    PubMed  CAS  Google Scholar 

  58. Christofori G, Naik P, Hanahan D. A second signal supplied by insulin-like growth factor II in oncogene-induced tumorigenesis. Nature. 1994;369:414–8. doi:10.1038/369414a0.

    Article  PubMed  CAS  Google Scholar 

  59. Christofori G, Naik P, Hanahan D. Deregulation of both imprinted and expressed alleles of the insulin-like growth factor 2 gene during beta-cell tumorigenesis. Nat Genet. 1995;10:196–201. doi:10.1038/ng0695-196.

    Article  PubMed  CAS  Google Scholar 

  60. Lopez T, Hanahan D. Elevated levels of IGF-1 receptor convey invasive and metastatic capability in a mouse model of pancreatic islet tumorigenesis. Cancer Cell. 2002;1:339–53. doi:10.1016/S1535-6108(02)00055-7.

    Article  PubMed  CAS  Google Scholar 

  61. Wu JD, Haugk K, Coleman I, Woodke L, Vessella R, Nelson P, et al. Combined in vivo effect of A12, a type 1 insulin-like growth factor receptor antibody, and docetaxel against prostate cancer tumors. Clin Cancer Res. 2006;12:6153–60. doi:10.1158/1078-0432.CCR-06-0443.

    Article  PubMed  CAS  Google Scholar 

  62. Plymate SR, Bae VL, Maddison L, Quinn LS, Ware JL. Reexpression of the type 1 insulin-like growth factor receptor inhibits the malignant phenotype of simian virus 40 T antigen immortalized human prostate epithelial cells. Endocrinology. 1997;138:1728–35. doi:10.1210/en.138.4.1728.

    Article  PubMed  CAS  Google Scholar 

  63. Plymate SR, Tennant MK, Culp SH, Woodke L, Marcelli M, Colman I, et al. Androgen receptor (AR) expression in AR-negative prostate cancer cells results in differential effects of DHT and IGF-I on proliferation and AR activity between localized and metastatic tumors. Prostate. 2004;61:276–90. doi:10.1002/pros.20099.

    Article  PubMed  CAS  Google Scholar 

  64. Scotlandi K, Maini C, Manara MC, Benini S, Serra M, Cerisano V, et al. Effectiveness of insulin-like growth factor I receptor antisense strategy against Ewing’s sarcoma cells. Cancer Gene Ther. 2002;9:296–307. doi:10.1038/sj.cgt.7700442.

    Article  PubMed  CAS  Google Scholar 

  65. Long L, Rubin R, Brodt P. Enhanced invasion and liver colonization by lung carcinoma cells overexpressing the type 1 insulin-like growth factor receptor. Exp Cell Res. 1998;238:116–21. doi:10.1006/excr.1997.3814.

    Article  PubMed  CAS  Google Scholar 

  66. Price JE, Polyzos A, Zhang RD, Daniels LM. Tumorigenicity and metastasis of human breast carcinoma cell lines in nude mice. Cancer Res. 1990;50:717–21.

    PubMed  CAS  Google Scholar 

  67. Leonessa F, Green D, Licht T, Wright A, Wingatelegette K, Lippman J, et al. MDA435/LCC6 and MDA435/LCC6(MDR1): ascites models of human breast cancer. Br J Cancer. 1996;73:154–61.

    PubMed  CAS  Google Scholar 

  68. Rae JM, Creighton CJ, Meck JM, Haddad BR, Johnson MD. MDA-MB-435 cells are derived from M14 melanoma cells—a loss for breast cancer, but a boon for melanoma research. Breast Cancer Res Treat. 2007;104:13–9. doi:10.1007/s10549-006-9392-8.

    Article  PubMed  Google Scholar 

  69. Barlund M, Monni O, Weaver JD, Kauraniemi P, Sauter G, Heiskanen M, et al. Cloning of BCAS3 (17q23) and BCAS4 (20q13) genes that undergo amplification, overexpression, and fusion in breast cancer. Genes Chromosomes Cancer. 2002;35:311–7. doi:10.1002/gcc.10121.

    Article  PubMed  CAS  Google Scholar 

  70. All-Ericsson C, Girnita L, Seregard S, Bartolazzi A, Jager MJ, Larsson O. Insulin-like growth factor-1 receptor in uveal melanoma: a predictor for metastatic disease and a potential therapeutic target. Invest Ophthalmol Vis Sci. 2002;43:1–8.

    PubMed  Google Scholar 

  71. Peyrat JP, Bonneterre J. Type 1 IGF receptor in human breast diseases. Breast Cancer Res Treat. 1992;22:59–67. doi:10.1007/BF01833334.

    Article  PubMed  CAS  Google Scholar 

  72. Railo MJ, von Smitten K, Pekonen F. The prognostic value of insulin-like growth factor-I in breast cancer patients. Results of a follow-up study on 126 patients. Eur J Cancer. 1994;3:307–11. doi:10.1016/0959-8049(94)90247-X.

    Article  Google Scholar 

  73. Peiro G, Benlloch S, Sanchez-Tejada L, Adrover E, Lerma E, Peiro FM, et al. Low activation of insulin-like growth factor 1-receptor (IGF1R) is associated with local recurrence in early breast carcinoma. Breast Cancer Res Treat 2008. doi:10.1007/s10549-008-0139-6.

  74. Creighton CJ, Casa A, Lazard Z, Huang S, Tsimelzon A, Hilsenbeck SG, et al. Insulin-like growth factor-I activates gene transcription programs strongly associated with poor breast cancer prognosis. J Clin Oncol. 2008;26:4078–85.

    Article  PubMed  CAS  Google Scholar 

  75. Dunn SE, Torres JV, Nihei N, Barrett JC. The insulin-like growth factor-1 elevates urokinase-type plasminogen activator-1 in human breast cancer cells: a new avenue for breast cancer therapy. Mol Carcinog. 2000;27:10–7. doi:10.1002/(SICI)1098-2744(200001)27:1<10::AID-MC3>3.0.CO;2-Z.

    Article  PubMed  CAS  Google Scholar 

  76. Ibrahim YH, Byron SA, Cui X, Lee AV, Yee D. Progesterone receptor-B regulation of insulin-like growth factor-stimulated cell migration in breast cancer cells via insulin receptor substrate-2. Mol Cancer Res. 2008;6:1491–8. doi:10.1158/1541-7786.MCR-07-2173.

    Article  PubMed  CAS  Google Scholar 

  77. Feng Y, Zhu Z, Xiao X, Choudhry V, Barrett JC, Dimitrov DS. Novel human monoclonal antibodies to insulin-like growth factor (IGF)-II that potently inhibit the IGF receptor type I signal transduction function. Mol Cancer Ther. 2006;5:114–20. doi:10.1158/1535-7163.MCT-05-0252.

    Article  PubMed  CAS  Google Scholar 

  78. Zhang D, Brodt P. Type 1 insulin-like growth factor regulates MT1-MMP synthesis and tumor invasion via PI 3-kinase/Akt signaling. Oncogene. 2003;22:974–82. doi:10.1038/sj.onc.1206197.

    Article  PubMed  CAS  Google Scholar 

  79. Bauer TW, Fan F, Liu W, Johnson M, Parikh NU, Parry GC, et al. Insulinlike growth factor-I-mediated migration and invasion of human colon carcinoma cells requires activation of c-Met and urokinase plasminogen activator receptor. Ann Surg. 2005;241:748–56. discussion 56–8. doi:10.1097/01.sla.0000160699.59061.92.

    Article  PubMed  Google Scholar 

  80. Dunn SE, Torres JV, Oh JS, Cykert DM, Barrett JC. Up-regulation of urokinase-type plasminogen activator by insulin-like growth factor-I depends upon phosphatidylinositol-3 kinase and mitogen-activated protein kinase kinase. Cancer Res. 2001;61:1367–74.

    PubMed  CAS  Google Scholar 

  81. Folkman J, Klagsbrun M. Angiogenic factors. Science. 1987;235:442–7. doi:10.1126/science.2432664.

    Article  PubMed  CAS  Google Scholar 

  82. Fidler IJ, Ellis LM. The implications of angiogenesis for the biology and therapy of cancer metastasis. Cell. 1994;79:185–8. doi:10.1016/0092-8674(94)90187-2.

    Article  PubMed  CAS  Google Scholar 

  83. Fidler IJ, Kumar R, Bielenberg DR, Ellis LM. Molecular determinants of angiogenesis in cancer metastasis. Cancer J Sci Am. 1998;4:S58–66.

    Google Scholar 

  84. Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 2003;3:721–32. doi:10.1038/nrc1187.

    Article  PubMed  CAS  Google Scholar 

  85. Miele C, Rochford JJ, Filippa N, Giorgetti-Peraldi S, Van Obberghen E. Insulin and insulin-like growth factor-I induce vascular endothelial growth factor mRNA expression via different signaling pathways. J Biol Chem. 2000;275:21695–702. doi:10.1074/jbc.M000805200.

    Article  PubMed  CAS  Google Scholar 

  86. Fukuda R, Hirota K, Fan F, Jung YD, Ellis LM, Semenza GL. 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. 2002;277:38205–11. doi:10.1074/jbc.M203781200.

    Article  PubMed  CAS  Google Scholar 

  87. Reinmuth N, Liu W, Fan F, Jung YD, Ahmad SA, Stoeltzing O, et al. Blockade of insulin-like growth factor I receptor function inhibits growth and angiogenesis of colon cancer. Clin Cancer Res. 2002;8:3259–69.

    PubMed  CAS  Google Scholar 

  88. Stoeltzing O, Liu W, Reinmuth N, Fan F, Parikh AA, Bucana CD, et al. Regulation of hypoxia-inducible factor-1alpha, vascular endothelial growth factor, and angiogenesis by an insulin-like growth factor-I receptor autocrine loop in human pancreatic cancer. Am J Pathol. 2003;163:1001–11.

    PubMed  CAS  Google Scholar 

  89. Carroll VA, Ashcroft M. Role of hypoxia-inducible factor (HIF)-1alpha versus HIF-2alpha in the regulation of HIF target genes in response to hypoxia, insulin-like growth factor-I, or loss of von Hippel–Lindau function: implications for targeting the HIF pathway. Cancer Res. 2006;66:6264–70. doi:10.1158/0008-5472.CAN-05-2519.

    Article  PubMed  CAS  Google Scholar 

  90. Achen MG, McColl BK, Stacker SA. Focus on lymphangiogenesis in tumor metastasis. Cancer Cell. 2005;7:121–7. doi:10.1016/j.ccr.2005.01.017.

    Article  PubMed  CAS  Google Scholar 

  91. Tang Y, Zhang D, Fallavollita L, Brodt P. Vascular endothelial growth factor C expression and lymph node metastasis are regulated by the type I insulin-like growth factor receptor. Cancer Res. 2003;63:1166–71.

    PubMed  CAS  Google Scholar 

  92. Bjorndahl M, Cao R, Nissen LJ, Clasper S, Johnson LA, Xue Y, et al. Insulin-like growth factors 1 and 2 induce lymphangiogenesis in vivo. Proc Natl Acad Sci U S A. 2005;102:15593–8. doi:10.1073/pnas.0507865102.

    Article  PubMed  CAS  Google Scholar 

  93. Baserga R, Peruzzi F, Reiss K. The IGF-1 receptor in cancer biology. Int J Cancer. 2003;107:873–7. doi:10.1002/ijc.11487.

    Article  PubMed  CAS  Google Scholar 

  94. Valentinis B, Morrione A, Peruzzi F, Prisco M, Reiss K, Baserga R. Anti-apoptotic signaling of the IGF-I receptor in fibroblasts following loss of matrix adhesion. Oncogene. 1999;18:1827–36. doi:10.1038/sj.onc.1202471.

    Article  PubMed  CAS  Google Scholar 

  95. Resnicoff M, Coppola D, Sell C, Rubin R, Ferrone S, Baserga R. Growth inhibition of human melanoma cells in nude mice by antisense strategies to the type 1 insulin-like growth factor receptor. Cancer Res. 1994;54:4848–50.

    PubMed  CAS  Google Scholar 

  96. Goya M, Miyamoto S, Nagai K, Ohki Y, Nakamura K, Shitara K, et al. Growth inhibition of human prostate cancer cells in human adult bone implanted into nonobese diabetic/severe combined immunodeficient mice by a ligand-specific antibody to human insulin-like growth factors. Cancer Res. 2004;64:6252–8. doi:10.1158/0008-5472.CAN-04-0919.

    Article  PubMed  CAS  Google Scholar 

  97. Zhang X, Yee D. Insulin-like growth factor binding protein-1 (IGFBP-1) inhibits breast cancer cell motility. Cancer Res. 2002;62:4369–75.

    PubMed  CAS  Google Scholar 

  98. van Golen CM, Schwab TS, Kim B, Soules ME, Su Oh S, Fung K, et al. Insulin-like growth factor-I receptor expression regulates neuroblastoma metastasis to bone. Cancer Res. 2006;66:6570–8. doi:10.1158/0008-5472.CAN-05-1448.

    Article  PubMed  Google Scholar 

  99. Sachdev D, Pelzer A, Zhang X, Gaillard-Kelly M, Yee D. Therapeutic inhibition of IGF-IR as an anti-metastatic therapy. Proceedings of the Endocrine Society 2008.

  100. de Bono JS, Attard G, Adjei A, Pollak MN, Fong PC, Haluska P, et al. Potential applications for circulating tumor cells expressing the insulin-like growth factor-I receptor. Clin Cancer Res. 2007;13:3611–6. doi:10.1158/1078-0432.CCR-07-0268.

    Article  PubMed  CAS  Google Scholar 

  101. Beloueche-Babari M, Jackson LE, Al-Saffar NM, Workman P, Leach MO, Ronen SM. Magnetic resonance spectroscopy monitoring of mitogen-activated protein kinase signaling inhibition. Cancer Res. 2005;65:3356–63.

    PubMed  CAS  Google Scholar 

  102. Meisamy S, Bolan PJ, Baker EH, Bliss RL, Gulbahce E, Everson LI, et al. Neoadjuvant chemotherapy of locally advanced breast cancer: predicting response with in vivo (1)H MR spectroscopy—a pilot study at 4 T. Radiology. 2004;233:424–31. doi:10.1148/radiol.2332031285.

    Article  PubMed  Google Scholar 

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Acknowledgement

The author thanks Douglas Yee from the Masonic Cancer Center, University of Minnesota for his helpful suggestions and review of this article.

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Correspondence to Deepali Sachdev.

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Sachdev, D. Regulation of Breast Cancer Metastasis by IGF Signaling. J Mammary Gland Biol Neoplasia 13, 431–441 (2008). https://doi.org/10.1007/s10911-008-9105-5

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