The Interaction of Insulin-Like Growth Factor Binding Protein 3 (IGFBP-3) in Insulin-Like Growth Factor (IGF)-Independent System

Document Type : Review Article

Authors

1 MSc Student, Department of Medical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

2 PhD Student, Department of Medical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

3 Associate Professor, Department of Medical Biochemistry, School of Pharmacy and Pharmaceutical Sciences AND Bioinformatics Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Insulin-like growth factor-binding protein 3 (IGFBP-3) is the most abundant IGFBP in circulation, interacts with high affinity to IGFs altering their function. Emerging evidence has indicated that IGFBP3 mostly involved in human disease such as diabetes, Alzheimer's disease, and cancer. It has been determined that IGFBP3 expression is decreased in various cancer cell lines by promoter methylation and proteases digestion. Therefore, bioavailable form of IGF-I increases in circulation promoting the tumorigenesis and progression of cancer. IGFBP3 function in cancer suppressing can be divided in two ways: IGF-dependent, and IGF-independent action. Recently it has been shown that IGFBP3 has vital roles independent of IGFs. Despite decades of unremitting research, this function of IGFBP-3 has not been clarified. However, it has been suggested that IGFBP3 independently can bind to its receptors in the nucleus including retinoid receptors (RXRs) peroxisome proliferator activated receptors (PPARγ), Nur77 vitamin D response (VDR), and/or cell surface receptors such as transmembrane protein 219 (TMEM219), low-density lipoprotein receptor-related protein 1 (LRP-1), and epidermal growth factor receptor (EGFR) inducing apoptosis. In this review, we described further mechanisms of IGF-independent action of IGFBP3.

Keywords

References

  1. Eyre H, Kahn R, Robertson RM, Clark NG, Doyle C, Hong Y, et al. Preventing cancer, cardiovascular disease, and diabetes: A common agenda for the American Cancer Society, the American Diabetes Association, and the American Heart Association. Circulation 2004; 109(25): 3244-55.
  2. Blackadar CB. Historical review of the causes of cancer. World J Clin Oncol 2016; 7(1): 54-86.
  3. Goossens N, Nakagawa S, Sun X, Hoshida Y. Cancer biomarker discovery and validation. Transl Cancer Res 2015; 4(3): 256-69.
  4. Ghosh I, Bhattacharjee D, Das AK, Chakrabarti G, Dasgupta A, Dey SK. Diagnostic Role of Tumour Markers CEA, CA15-3, CA19-9 and CA125 in Lung Cancer. Indian J Clin Biochem 2013; 28(1): 24-9.
  5. Kajani AA, Mofid MR, Abolfazli K, Tafreshi SA. Encapsulated activated charcoal as a potent agent for improving taxane synthesis and recovery from cultures.
  6. Biotechnol Appl Biochem 2010; 56(2): 71-6.
  7. Kajani AA, Moghim S, Mofid MR. Optimization of the basal medium for improving production and secretion of taxanes from suspension cell culture of Taxus baccata L. Daru 2012; 20(1): 54.
  8. Akbari V, Moghim S, Reza MM. Comparison of epothilone and taxol binding in yeast tubulin using molecular modeling. Avicenna J Med Biotechnol 2011; 3(4): 167-75.
  9. Laron Z. Insulin-like growth factor 1 (IGF-1): A growth hormone. Mol Pathol 2001; 54(5): 311-6.
  10. Khodadadi E, Ataei N, Mofid MR. The effect and mechanism of action of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in human breast cancer; a systematic review. J Isfahan Med Sch 2013; 31(254): 1560-7. [In Persian].
  11. Christopoulos PF, Msaouel P, Koutsilieris M. The role of the insulin-like growth factor-1 system in breast cancer. Mol Cancer 2015; 14: 43.
  12. Moschos SJ, Mantzoros CS. The role of the IGF system in cancer: From basic to clinical studies and clinical applications. Oncology 2002; 63(4): 317-32.
  13. Mecasermin rinfabate: Insulin-like growth factor-I/insulin-like growth factor binding protein-3, mecaserimin rinfibate, rhIGF-I/rhIGFBP-3. Drugs R D 2005; 6(2): 120-7.
  14. Jafari S, Babaeipour V, Seyedi HA, Rahaie M, Mofid MR, Haddad L, et al. Recombinant production of mecasermin in E. coli expression system. Res Pharm Sci 2014; 9(6): 453-61.
  15. Ranjbari J, Babaeipour V, Vahidi H, Moghimi H, Mofid MR, Namvaran MM, et al. Enhanced production of insulin-like growth factor i protein in Escherichia coli by optimization of five key factors. Iran J Pharm Res 2015; 14(3): 907-17.
  16. Khodadadi E, Panjepour M, Abbasian M, Broujeni ZK, Mofid MR. Cloning and expression of full-length human insulin-like growth factor binding protein 3 (IGFBP3) in the Escherichia coli. Adv Biomed Res 2015; 4: 66.
  17. Werner H, Weinstein D, Bentov I. Similarities and differences between insulin and IGF-I: structures, receptors, and signalling pathways. Arch Physiol Biochem 2008; 114(1): 17-22.
  18. Siddle K. Signalling by insulin and IGF receptors: supporting acts and new players. J Mol Endocrinol 2011; 47(1): R1-10.
  19. Laviola L, Natalicchio A, Giorgino F. The IGF-I signaling pathway. Curr Pharm Des 2007; 13(7): 663-9.
  20. Denduluri SK, Idowu O, Wang Z, Liao Z, Yan Z, Mohammed MK, et al. Insulin-like growth factor (IGF) signaling in tumorigenesis and the development of cancer drug resistance. Genes Dis 2015; 2(1): 13-25.
  21. Clemmons DR. Role of IGF binding proteins in regulating metabolism. Trends Endocrinol Metab 2016; 27(6): 375-91.
  22. Forbes BE, McCarthy P, Norton RS. Insulin-like growth factor binding proteins: a structural perspective. Front Endocrinol (Lausanne ) 2012; 3: 38.
  23. Daza DO, Sundstrom G, Bergqvist CA, Duan C, Larhammar D. Evolution of the insulin-like growth factor binding protein (IGFBP) family. Endocrinology 2011; 152(6): 2278-89.
  24. Cubbage ML, Suwanichkul A, Powell DR. Insulin-like growth factor binding protein-3. Organization of the human chromosomal gene and demonstration of promoter activity. J Biol Chem 1990; 265(21): 12642-9.
  25. Ranke MB. Insulin-like growth factor binding-protein-3 (IGFBP-3). Best Pract Res Clin Endocrinol Metab 2015; 29(5): 701-11.
  26. Singh B, Charkowicz D, Mascarenhas D. Insulin-like growth factor-independent effects mediated by a C-terminal metal-binding domain of insulin-like growth factor binding protein-3. J Biol Chem 2004; 279(1): 477-87.
  27. Baxter RC. IGF binding proteins in cancer: Mechanistic and clinical insights. Nat Rev Cancer 2014; 14(5): 329-41.
  28. Firth SM, Baxter RC. Characterisation of recombinant glycosylation variants of insulin-like growth factor binding protein-3. J Endocrinol 1999; 160(3): 379-87.
  29. Baricevic I, Masnikosa R, Lagundzin D, Golubovic V, Nedic O. Alterations of insulin-like growth factor binding protein 3 (IGFBP-3) glycosylation in patients with breast tumours. Clin Biochem 2010; 43(9): 725-31.
  30. Coverley JA, Baxter RC. Phosphorylation of insulin-like growth factor binding proteins. Mol Cell Endocrinol 1997; 128(1-2): 1-5.
  31. Yamada PM, Lee KW. Perspectives in mammalian IGFBP-3 biology: local vs. systemic action. Am J Physiol Cell Physiol 2009; 296(5): C954-C976.
  32. Perks CM, Holly JM. Epigenetic regulation of insulin-like growth factor binding protein-3 (IGFBP-3) in cancer. J Cell Commun Signal 2015; 9(2): 159-66.
  33. Helle SI, Geisler S, Aas T, Paulsen T, Holly JM, Lonning PE. Plasma insulin-like growth factor binding protein-3 proteolysis is increased in primary breast cancer. Br J Cancer 2001; 85(1): 74-7.
  34. Booth BA, Boes M, Bar RS. IGFBP-3 proteolysis by plasmin, thrombin, serum: Heparin binding, IGF binding, and structure of fragments. Am J Physiol 1996; 271(3 Pt 1): E465-E470.
  35. Gigek CO, Leal MF, Lisboa LC, Silva PN, Chen ES, Lima EM, et al. Insulin-like growth factor binding protein-3 gene methylation and protein expression in gastric adenocarcinoma. Growth Horm IGF Res 2010; 20(3): 234-8.
  36. Yu H, Rohan T. Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst 2000; 92(18): 1472-89.
  37. Tripathi G, Salih DA, Drozd AC, Cosgrove RA, Cobb LJ, Pell JM. IGF-independent effects of insulin-like growth factor binding protein-5 (IGFBP5) in vivo. FASEB J 2009; 23(8): 2616-26.
  38. Oh Y. IGF-independent regulation of breast cancer growth by IGF binding proteins. Breast Cancer Res Treat 1998; 47(3): 283-93.
  39. Vestey SB, Perks CM, Sen C, Calder CJ, Holly JM, Winters ZE. Immunohistochemical expression of insulin-like growth factor binding protein-3 in invasive breast cancers and ductal carcinoma in situ: implications for clinicopathology and patient outcome. Breast Cancer Res 2005; 7(1): R119-R129.
  40. Takaoka M, Kim SH, Okawa T, Michaylira CZ, Stairs DB, Johnstone CN, et al. IGFBP-3 regulates esophageal tumor growth through IGF-dependent and independent mechanisms. Cancer Biol Ther 2007; 6(4): 534-40.
  41. Oh Y, Muller HL, Lamson G, Rosenfeld RG. Insulin-like growth factor (IGF)-independent action of IGF-binding protein-3 in Hs578T human breast cancer cells. Cell surface binding and growth inhibition. J Biol Chem 1993; 268(20): 14964-71.
  42. Lee KW, Liu B, Ma L, Li H, Bang P, Koeffler HP, et al. Cellular internalization of insulin-like growth factor binding protein-3: distinct endocytic pathways facilitate re-uptake and nuclear localization. J Biol Chem 2004; 279(1): 469-76.
  43. Micutkova L, Hermann M, Offterdinger M, Hess MW, Matscheski A, Pircher H, et al. Analysis of the cellular uptake and nuclear delivery of insulin-like growth factor binding protein-3 in human osteosarcoma cells. Int J Cancer 2012; 130(7): 1544-57.
  44. Schedlich LJ, Le Page SL, Firth SM, Briggs LJ, Jans DA, Baxter RC. Nuclear import of insulin-like growth factor-binding protein-3 and -5 is mediated by the importin beta subunit. J Biol Chem 2000; 275(31): 23462-70.
  45. Evans RM, Mangelsdorf DJ. Nuclear Receptors, RXR, and the Big Bang. Cell 2014; 157(1): 255-66.
  46. Wei LN. Retinoid receptors and their coregulators. Annu Rev Pharmacol Toxicol 2003; 43: 47-72.
  47. Lee KW, Ma L, Yan X, Liu B, Zhang XK, Cohen P. Rapid apoptosis induction by IGFBP-3 involves an insulin-like growth factor-independent nucleomitochondrial translocation of RXRalpha/Nur77. J Biol Chem 2005; 280(17): 16942-8.
  48. Liu B, Lee HY, Weinzimer SA, Powell DR, Clifford JL, Kurie JM, et al. Direct functional interactions between insulin-like growth factor-binding protein-3 and retinoid X receptor-alpha regulate transcriptional signaling and apoptosis. J Biol Chem 2000; 275(43): 33607-13.
  49. Tyagi S, Gupta P, Saini AS, Kaushal C, Sharma S. The peroxisome proliferator-activated receptor: A family of nuclear receptors role in various diseases. J Adv Pharm Technol Res 2011; 2(4): 236-40.
  50. Lefterova MI, Haakonsson AK, Lazar MA, Mandrup S. PPARgamma and the global map of adipogenesis and beyond. Trends Endocrinol Metab 2014; 25(6): 293-302.
  51. Chan SS, Schedlich LJ, Twigg SM, Baxter RC. Inhibition of adipocyte differentiation by insulin-like growth factor-binding protein-3. Am J Physiol Endocrinol Metab 2009; 296(4): E654-E663.
  52. Pon CK, Firth SM, Baxter RC. Involvement of insulin-like growth factor binding protein-3 in peroxisome proliferator-activated receptor gamma-mediated inhibition of breast cancer cell growth. Mol Cell Endocrinol 2015; 399: 354-61.
  53. Kim SY, Kim MS, Lee MK, Kim JS, Yi HK, Nam SY, et al. PPARgamma induces growth inhibition and apoptosis through upregulation of insulin-like growth factor-binding protein-3 in gastric cancer cells. Braz J Med Biol Res 2015; 48(3): 226-33.
  54. Safe S, Kim K, Li X, Lee S. NR4A orphan receptors and cancer. Nucl Recept Signal 2011; 9: e002.
  55. Hsu HC, Zhou T, Mountz JD. Nur77 family of nuclear hormone receptors. Curr Drug Targets Inflamm Allergy 2004; 3(4): 413-23.
  56. To SK, Zeng JZ, Wong AS. Nur77: A potential therapeutic target in cancer. Expert Opin Ther Targets 2012; 16(6): 573-85.
  57. Lee KW, Cobb LJ, Paharkova-Vatchkova V, Liu B, Milbrandt J, Cohen P. Contribution of the orphan nuclear receptor Nur77 to the apoptotic action of IGFBP-3. Carcinogenesis 2007; 28(8): 1653-8.
  58. Agostini-Dreyer A, Jetzt AE, Stires H, Cohick WS. Endogenous IGFBP-3 mediates intrinsic apoptosis through modulation of Nur77 phosphorylation and nuclear export. Endocrinology 2015; 156(11): 4141-51.
  59. Fleet JC, DeSmet M, Johnson R, Li Y. Vitamin D and cancer: A review of molecular mechanisms. Biochem J 2012; 441(1): 61-76.
  60. Carlberg C, Campbell MJ. Vitamin D receptor signaling mechanisms: Integrated actions of a well-defined transcription factor. Steroids 2013; 78(2): 127-36.
  61. Haussler MR, Haussler CA, Bartik L, Whitfield GK, Hsieh JC, Slater S, et al. Vitamin D receptor: molecular signaling and actions of nutritional ligands in disease prevention. Nutr Rev 2008; 66(10 Suppl 2): S98-112.
  62. Li J, Jin D, Fu S, Mei G, Zhou J, Lei L, et al. Insulin-like growth factor binding protein-3 modulates osteoblast differentiation via interaction with vitamin D receptor. Biochem Biophys Res Commun 2013; 436(4): 632-7.
  63. Malinen M, Ryynanen J, Heinaniemi M, Vaisanen S, Carlberg C. Cyclical regulation of the insulin-like growth factor binding protein 3 gene in response to 1alpha,25-dihydroxyvitamin D3. Nucleic Acids Res 2011; 39(2): 502-12.
  64. Kim JH, Choi DS, Lee OH, Oh SH, Lippman SM, Lee HY. Antiangiogenic antitumor activities of IGFBP-3 are mediated by IGF-independent suppression of Erk1/2 activation and Egr-1-mediated transcriptional events. Blood 2011; 118(9): 2622-31.
  65. Hague A, Manning AM, Hanlon KA, Huschtscha LI, Hart D, Paraskeva C. Sodium butyrate induces apoptosis in human colonic tumour cell lines in a p53-independent pathway: implications for the possible role of dietary fibre in the prevention of large-bowel cancer. Int J Cancer 1993; 55(3): 498-505.
  66. Collard TJ, Guy M, Butt AJ, Perks CM, Holly JM, Paraskeva C, et al. 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 2003; 24(3): 393-401.
  67. Spagnoli A, Torello M, Nagalla SR, Horton WA, Pattee P, Hwa V, et al. Identification of STAT-1 as a molecular target of IGFBP-3 in the process of chondrogenesis. J Biol Chem 2002; 277(21): 18860-7.
  68. Shahjee HM, Kefas B, Bhattacharyya N, Radwan MK. Signal Transduction Pathways Mediated by Secreted and Non-secreted Forms of intact Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) and its 1-97 N-terminal Fragment in PC-3 Human Prostate Cancer Cells. J Cancer Ther 2013; 4(8).
  69. Bhattacharyya N, Pechhold K, Shahjee H, Zappala G, Elbi C, Raaka B, et al. Nonsecreted insulin-like growth factor binding protein-3 (IGFBP-3) can induce apoptosis in human prostate cancer cells by IGF-independent mechanisms without being concentrated in the nucleus. J Biol Chem 2006; 281(34): 24588-601.
  70. Natsuizaka M, Kinugasa H, Kagawa S, Whelan KA, Naganuma S, Subramanian H, et al. IGFBP3 promotes esophageal cancer growth by suppressing oxidative stress in hypoxic tumor microenvironment. Am J Cancer Res 2014; 4(1): 29-41.
  71. Hoesel B, Schmid JA. The complexity of NF-kappaB signaling in inflammation and cancer. Mol Cancer 2013; 12: 86.
  72. Han J, Jogie-Brahim S, Harada A, Oh Y. Insulin-like growth factor-binding protein-3 suppresses tumor growth via activation of caspase-dependent apoptosis and cross-talk with NF-kappaB signaling. Cancer Lett 2011; 307(2): 200-10.
  73. Naspi A, Panasiti V, Abbate F, Roberti V, Devirgiliis V, Curzio M, et al. Insulin-like-growth-factor-binding-protein-3 (IGFBP-3) contrasts melanoma progression in vitro and in vivo. PLoS One 2014; 9(6): e98641.
  74. El-Deiry WS. The role of p53 in chemosensitivity and radiosensitivity. Oncogene 2003; 22(47):
  75. -95.
  76. Bieging KT, Mello SS, Attardi LD. Unravelling mechanisms of p53-mediated tumour suppression. Nat Rev Cancer 2014; 14(5): 359-70.
  77. Rajah R, Valentinis B, Cohen P. Insulin-like growth factor (IGF)-binding protein-3 induces apoptosis and mediates the effects of transforming growth factor-beta1 on programmed cell death through a p53- and IGF-independent mechanism. J Biol Chem 1997; 272(18): 12181-8.
  78. Leal SM, Huang SS, Huang JS. Interactions of high affinity insulin-like growth factor-binding proteins with the type V transforming growth factor-beta receptor in mink lung epithelial cells. J Biol Chem 1999; 274(10): 6711-7.
  79. Massague J. TGFbeta signalling in context. Nat Rev Mol Cell Biol 2012; 13(10): 616-30.
  80. Fanayan S, Firth SM, Butt AJ, Baxter RC. Growth inhibition by insulin-like growth factor-binding protein-3 in T47D breast cancer cells requires transforming growth factor-beta (TGF-beta ) and the type II TGF-beta receptor. J Biol Chem 2000; 275(50): 39146-51.
  81. Lillis AP, Van Duyn LB, Murphy-Ullrich JE, Strickland DK. LDL receptor-related protein 1: unique tissue-specific functions revealed by selective gene knockout studies. Physiol Rev 2008; 88(3): 887-918.
  82. Huang SS, Ling TY, Tseng WF, Huang YH, Tang FM, Leal SM, et al. Cellular growth inhibition by IGFBP-3 and TGF-beta1 requires LRP-1. FASEB J 2003; 17(14): 2068-81.
  83. Pampusch MS, Kamanga-Sollo E, Hathaway MR, White ME, Dayton WR. Low-density lipoprotein-related receptor protein 1 (LRP-1) is not required for insulin-like growth factor binding protein 3 (IGFBP-3) to suppress L6 myogenic cell proliferation. Domest Anim Endocrinol 2011; 40(4): 197-204.
  84. Grkovic S, O'Reilly VC, Han S, Hong M, Baxter RC, Firth SM. IGFBP-3 binds GRP78, stimulates autophagy and promotes the survival of breast cancer cells exposed to adverse microenvironments. Oncogene 2013; 32(19): 2412-20.
  85. Lomax ME, Folkes LK, O'Neill P. Biological consequences of radiation-induced DNA damage: relevance to radiotherapy. Clin Oncol (R Coll Radiol) 2013; 25(10): 578-85.
  86. Rastogi RP, Richa, Kumar A, Tyagi MB, Sinha RP. Molecular mechanisms of ultraviolet radiation-induced DNA damage and repair. J Nucleic Acids 2010; 2010: 592980.
  87. Achary MP, Jaggernauth W, Gross E, Alfieri A, Klinger HP, Vikram B. Cell lines from the same cervical carcinoma but with different radiosensitivities exhibit different cDNA microarray patterns of gene expression. Cytogenet Cell Genet 2000; 91(1-4): 39-43.
  88. Zhao L, He LR, Xi M, Cai MY, Shen JX, Li QQ, et al. Nimotuzumab promotes radiosensitivity of EGFR-overexpression esophageal squamous cell carcinoma cells by upregulating IGFBP-3. J Transl Med 2012; 10: 249.
  89. Lin MZ, Marzec KA, Martin JL, Baxter RC. The role of insulin-like growth factor binding protein-3 in the breast cancer cell response to DNA-damaging agents. Oncogene 2014; 33(1): 85-96.
  90. Ingermann AR, Yang YF, Han J, Mikami A, Garza AE, Mohanraj L, et al. Identification of a novel cell death receptor mediating IGFBP-3-induced anti-tumor effects in breast and prostate cancer. J Biol Chem 2010; 285(39): 30233-46.
  91. Kashyap MK. Role of insulin-like growth factor-binding proteins in the pathophysiology and tumorigenesis of gastroesophageal cancers. Tumour Biol 2015; 36(11): 8247-57.
  92. D'Addio F, La RS, Maestroni A, Jung P, Orsenigo E, Ben NM, et al. Circulating IGF-I and IGFBP3 Levels Control Human Colonic Stem Cell Function and Are Disrupted in Diabetic Enteropathy. Cell Stem Cell 2015; 17(4): 486-98.
  93. Cheng CW, Yilmaz OH. IGFBP3 and T1D: Systemic Factors in Colonic Stem Cell Function and Diabetic Enteropathy. Cell Stem Cell 2015; 17(4): 379-80.
Journal of Isfahan Medical School
Volume 35, Issue 451 - Serial Number 451
September and October 2017
Pages 1452-1461

Files

History

  • Receive Date: 25 September 2017
  • Revise Date: 01 November 2024
  • Accept Date: 06 April 2022

Share

How to cite

Statistics