IGFBP-2: The dark horse in metabolism and cancer

Cytokine and Growth Factor Reviews

Volumn 26, Issue 3, 2015, Pages 329-346

  Russo, V C ^a,b   Azar, W J ^a,c   Yau, S W ^b   Sabin, M A ^a,b   Werther, G A ^a,b  

^a ROYAL CHILDREN'S HOSPITAL   (Australia)

^b UNIVERSITY OF MELBOURNE   (Australia)

^c PETER MACCALLUM CANCER CENTRE   (Australia)

Author keywords

Cancer; Diabetes; IGFBP 2; Metabolism; Obesity

Indexed keywords

ARGININE; ASPARTIC ACID; GLYCINE; INSULIN RECEPTOR; INTEGRIN RECEPTOR; PROTEOGLYCAN; REGULATOR PROTEIN; SOMATOMEDIN; SOMATOMEDIN BINDING PROTEIN; SOMATOMEDIN BINDING PROTEIN 2; SOMATOMEDIN RECEPTOR; TRANSCRIPTION FACTOR;

BODY GROWTH; BONE DENSITY; BONE GROWTH; BREAST CANCER; CANCER GROWTH; CANCER THERAPY; CELL SURFACE; CYTOPLASM; DIABETES MELLITUS; EXERCISE; EXTRACELLULAR MATRIX; GENE LOCATION; GLIOMA; HEPARIN BINDING DOMAIN; HORMONAL REGULATION; HUMAN; IGFBP 2 GENE; IN VIVO STUDY; INTEGRIN BINDING DOMAIN; INTRACELLULAR SIGNALING; KNOCKOUT MOUSE; METABOLISM; NEOPLASM; NONHUMAN; NUCLEAR LOCALIZATION SIGNAL; NUTRITION; OBESITY; OSSIFICATION; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; REVIEW; TRAINING; TRANSCRIPTION INITIATION; TRANSGENIC MOUSE; ANIMAL;

ANIMALIA; EQUIDAE; MUS; MUS MUSCULUS;

ANIMALS; HUMANS; INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN 2; NEOPLASMS; SOMATOMEDINS;

EID: 84929655860     PISSN: 13596101     EISSN: 18790305     Source Type: Journal    
DOI: 10.1016/j.cytogfr.2014.12.001     Document Type: Review

References (218)

1. Zapf J., Froesch E.R. Insulin-like growth factors/somatomedins: structure, secretion, biological actions and physiological role. Horm Res 1986, 24:121-130.
2. Daughaday W.H., Rotwein P. Insulin-like growth factors I and II, peptide messenger ribonucleic acid and gene structures, serum, and tissue concentrations. Endocr Rev 1989, 10:68-91.
3. Han V.K., D'Ercole A.J., Lund P.K. Cellular localization of somatomedin (insulin-like growth factor) messenger RNA in the human fetus. Science 1987, 236:193-197.
4. Murphy L.J., Bell G.I., Friesen H.G. Tissue distribution of insulin-like growth factor I and II messenger ribonucleic acid in the adult rat. Endocrinology 1987, 120:1279-1282.
5. Russo V.C., Gluckman P., Feldman E.L., Werther G.A. The insulin-like growth factor system and its pleiotropic functions in brain. Endocr Rev 2005, 26:916-943.
6. Daughaday W.H. Somatomedin: proposed designation for sulphation factor. Nature 1972, 235:107.
7. Kaplan S.A., Cohen P. Review: The somatomedin hypothesis 2007: 50 years later. J Clin Endocrinol Metab 2007, 92:4529-4535.
8. Liu J.P., Baker J., Perkins A.S., Robertson E.J., Efstratiadis A. Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell 1993, 75:59-72.
9. De Chiara T.M., Efstratiadis A., Robertson E.J. A growth-deficiency phenotype in heterozygous mice carrying an insulin-like growth factor II gene disrupted by targeting. Nature 1990, 345:78-80.
10. LeRoith D., Werner H., Neuenschwander S., Kalebic T., Helman L.J. The role of the insulin-like growth factor-I receptor in cancer. Ann N Y Acad Sci 1995, 766:402-408.
11. Behringer R.R., Lewin T.M., Quaife C.J., Palmiter R.D., Brinster R.L., D'Ercole A.J. Expression of insulin-like growth factor I stimulates normal somatic growth in growth hormone-deficient transgenic mice. Endocrinology 1990, 127:1033-1040.
12. Yanochko G.M., Eckhart W. Type I insulin-like growth factor receptor over-expression induces proliferation and anti-apoptotic signaling in a three-dimensional culture model of breast epithelial cells. Breast Cancer Res 2006, 8:R18.
13. Sepp-Lorenzino L. Structure and function of the insulin-like growth factor I receptor. Breast Cancer Res Treat 1998, 47:235-253.
14. Milazzo G., Yip C.C., Maddux B.A., Vigneri R., Goldfine I.D. High-affinity insulin binding to an atypical insulin-like growth factor-I receptor in human breast cancer cells. J Clin Invest 1992, 89:899-908.
15. Moxham C.P., Duronio V., Jacobs S. Insulin-like growth factor I receptor beta-subunit heterogeneity. Evidence for hybrid tetramers composed of insulin-like growth factor I and insulin receptor heterodimers. J Biol Chem 1989, 264:13238-13244.
16. Siddle K., Soos M.A., Field C.E., Nave B.T. Hybrid and atypical insulin/insulin-like growth factor I receptors. Horm Res 1994, 41(Suppl. 2):56-64. (Review, 44 refs).
17. Sakano K., Enjoh T., Numata F., Fujiwara H., Marumoto Y., Higashihashi N., et al. The design, expression, and characterization of human insulin-like growth factor II (IGF-II) mutants specific for either the IGF-II/cation-independent mannose 6-phosphate receptor or IGF-I receptor. J Biol Chem 1991, 266:20626-20635.
18. Braulke T. Type-2 IGF receptor: a multi-ligand binding protein. Horm Metab Res 1999, 31:242-246.
19. Baker J., Liu J.P., Robertson E.J., Efstratiadis A. Role of insulin-like growth factors in embryonic and postnatal growth. Cell 1993, 75:73-82.
20. Ludwig R.L., Bates S., Vousden K.H. Differential activation of target cellular promoters by p53 mutants with impaired apoptotic function. Mol Cell Biol 1996, 16:4952-4960.
21. Louvi A., Accili D., Efstratiadis A. Growth-promoting interaction of IGF-II with the insulin receptor during mouse embryonic development. Dev Biol 1997, 189:33-48.
22. Morrione A., Valentinis B., Xu S.Q., Yumet G., Louvi A., Efstratiadis A., et al. Insulin-like growth factor II stimulates cell proliferation through the insulin receptor. Proc Natl Acad Sci U S A 1997, 94:3777-3782.
23. Belfiore A., Frasca F., Pandini G., Sciacca L., Vigneri R. Insulin receptor isoforms and insulin receptor/insulin-like growth factor receptor hybrids in physiology and disease. Endocr Rev 2009, 30:586-623.
24. Firth S.M., Baxter R.C. Cellular actions of the insulin-like growth factor binding proteins. Endocr Rev 2002, 23:824-854.
25. Daza D.O., Sundström G., Bergqvist C.A., Duan C., Larhammar D. Evolution of the insulin-like growth factor binding protein (IGFBP) family. Endocrinology 2011, 152:2278-2289.
26. Baxter R.C. Insulin-like growth factor (IGF) binding proteins: the role of serum IGFBPs in regulating IGF availability. Acta Paediatr Scand Suppl 1991, 372:107-114. (Review, 45 refs).
27. Baxter R.C. Insulin-like growth factor binding proteins in the human circulation: a review. Horm Res 1994, 42:140-144. (Review, 44 refs).
28. Barreca A., Ponzani P., Arvigo A., Voci A., Giordano G., Minuto F. Functions and regulation of the acid-labile subunit of the 150K complex. Prog Growth Factor Res 1995, 6:231-239.
29. Twigg S.M., Kiefer M.C., Zapf J., Baxter R.C. A central domain binding site in insulin-like growth factor binding protein-5 for the acid-labile subunit. Endocrinology 2000, 141:454-457.
30. Baxter R.C., Cowell C.T. Diurnal rhythm of growth hormone-independent binding protein for insulin-like growth factors in human plasma. J Clin Endocrinol Metab 1987, 65:432-440.
31. Giudice L.C., Farrell E.M., Pham H., Lamson G., Rosenfeld R.G. Insulin-like growth factor binding proteins in maternal serum throughout gestation and in the puerperium: effects of a pregnancy-associated serum protease activity. J Clin Endocrinol Metab 1990, 71:806-816.
32. Zapf J., Schmid C., Guler H.P., Waldvogel M., Hauri C., Futo E., et al. Regulation of binding proteins for insulin-like growth factors (IGF) in humans. Increased expression of IGF binding protein 2 during IGF I treatment of healthy adults and in patients with extrapancreatic tumor hypoglycemia. J Clin Invest 1990, 86:952-961.
33. Clemmons D.R., Thissen J.P., Maes M., Ketelslegers J.M., Underwood L.E. Insulin-like growth factor-I (IGF-I) infusion into hypophysectomized or protein-deprived rats induces specific IGF-binding proteins in serum. Endocrinology 1989, 125:2967-2972.
34. Binkert C., Landwehr J., Mary J.L., Schwander J., Heinrich G. Cloning, sequence analysis and expression of a cDNA encoding a novel insulin-like growth factor binding protein (IGFBP-2). EMBO J 1989, 8:2497-2502.
35. Galea C.A., Mobli M., McNeil K.A., Mulhern T.D., Wallace J.C., King G.F., et al. Insulin-like growth factor binding protein-2: NMR analysis and structural characterization of the N-terminal domain. Biochimie 2012, 94:608-616.
36. Forbes B.E., Turner D., Hodge S.J., McNeil K.A., Forsberg G., Wallace J.C. Localization of an insulin-like growth factor (IGF) binding site of bovine IGF binding protein-2 using disulfide mapping and deletion mutation analysis of the C-terminal domain. J Biol Chem 1998, 273:4647-4652.
37. Ho P.J., Baxter R.C. Insulin-like growth factor-binding protein-2 in patients with prostate carcinoma and benign prostatic hyperplasia. Clin Endocrinol (Oxf) 1997, 46:333-342.
38. Russo V.C., Rekaris G., Baker N.L., Bach L.A., Werther G.A. Basic fibroblast growth factor induces proteolysis of secreted and cell membrane-associated insulin-like growth factor binding protein-2 in human neuroblastoma cells. Endocrinology 1999, 140:3082-3090.
39. Hobba G.D., Forbes B.E., Parkinson E.J., Francis G.L., Wallace J.C. The insulin-like growth factor (IGF) binding site of bovine insulin-like growth factor binding protein-2 (bIGFBP-2) probed by iodination. J Biol Chem 1996, 271:30529-30536.
40. Carrick F.E., Hinds M.G., McNeil K.A., Wallace J.C., Forbes B.E., Norton R.S. Interaction of insulin-like growth factor (IGF)-I and -II with IGF binding protein-2: mapping the binding surfaces by nuclear magnetic resonance. J Mol Endocrinol 2005, 34:685-698.
41. Graham M.E., Kilby D.M., Firth S.M., Robinson P.J., Baxter R.C. The in vivo phosphorylation and glycosylation of human insulin-like growth factor-binding protein-5. Mol Cell Proteomics 2007, 6:1392-1405.
42. Coverley J.A., Baxter R.C. Phosphorylation of insulin-like growth factor binding proteins. Mol Cell Endocrinol 1997, 128:1-5. (Review, 25 refs).
43. Song S.W., Fuller G.N., Khan A., Kong S., Shen W., Taylor E., et al. IIp45, an insulin-like growth factor binding protein 2 (IGFBP-2) binding protein, antagonizes IGFBP-2 stimulation of glioma cell invasion. Proc Natl Acad Sci U S A 2003, 100:13970-13975.
44. Frommer K.W., Reichenmiller K., Schutt B.S., Hoeflich A., Ranke M.B., Dodt G., et al. IGF-independent effects of IGFBP-2 on the human breast cancer cell line Hs578T. J Mol Endocrinol 2006, 37:13-23. 10.1677/jme.1.01955.
45. Pereira J.J., Meyer T., Docherty S.E., Reid H.H., Marshall J., Thompson E.W., et al. Bimolecular interaction of insulin-like growth factor (IGF) binding protein-2 with alphavbeta3 negatively modulates IGF-I-mediated migration and tumor growth. Cancer Res 2004, 64:977-984.
46. Perks C.M., Vernon E.G., Rosendahl A.H., Tonge D., Holly J.M. IGF-II and IGFBP-2 differentially regulate PTEN in human breast cancer cells. Oncogene 2007, 26:5966-5972.
47. Foulstone E.J., Zeng L., Perks C.M., Holly J.M. Insulin-like growth factor binding protein 2 (IGFBP-2) promotes growth and survival of breast epithelial cells: novel regulation of the estrogen receptor. Endocrinology 2013, 154(May (5)):1780-1793.
48. Cardin A.D., Weintraub H.J. Molecular modeling of protein-glycosaminoglycan interactions. Arteriosclerosis 1989, 9:21-32.
49. Russo V.C., Schutt B.S., Andaloro E., Ymer S.I., Hoeflich A., Ranke M.B., et al. Insulin-like growth factor binding protein-2 binding to extracellular matrix plays a critical role in neuroblastoma cell proliferation, migration, and invasion. Endocrinology 2005, 146:4445-4455. 10.1210/en.2005-0467.
50. Shen X., Xi G., Maile L.A., Wai C., Rosen C.J., Clemmons D.R. Insulin-like growth factor binding protein-2 functions coordinately with receptor protein tyrosine phosphatase beta and the IGF-I receptor to regulate IGF-I-stimulated signaling. Mol Cell Biol 2012, 32(October (20)):4116-4130.
51. Kuang Z., Yao S., Keizer D.W., Wang C.C., Bach L.A., Forbes B.E., et al. Structure, dynamics and heparin binding of the C-terminal domain of insulin-like growth factor-binding protein-2 (IGFBP-2). J Mol Biol 2006, 364:690-704.
52. Arai T., Busby W., Clemmons D.R. Binding of insulin-like growth factor (IGF) I or II to IGF-binding protein-2 enables it to bind to heparin and extracellular matrix. Endocrinology 1996, 137:4571-4575.
53. Russo V.C., Bach L.A., Fosang A.J., Baker N.L., Werther G.A. Insulin-like growth factor binding protein-2 binds to cell surface proteoglycans in the rat brain olfactory bulb. Endocrinology 1997, 138:4858-4867.
54. Russo V.C., Bach L.A., Werther G.A. Cell membrane association of insulin-like growth factor binding protein-2 (IGFBP-2) in the rat brain olfactory bulb. Prog Growth Factor Res 1995, 6:329-336.
55. Russo V.C., Schutt B.S., Andaloro E., Ymer S.I., Hoeflich A., Fosang A., et al. IGFBP-2/IGF-I/proteoglycan complexes in the rat brain olfactory bulb. 12th International congress of endocrinology Medimont international proceedings 2004, 817-820. ISBN 88-7587-071-3.
56. DeMambro V.E., Maile L., Wai C., Kawai M., Cascella T., Rosen C.J., et al. Insulin-like growth factor-binding protein-2 is required for osteoclast differentiation. J Bone Miner Res 2012, 27:390-400.
57. Besnard V., Corroyer S., Trugnan G., Chadelat K., Nabeyrat E., Cazals V., et al. Distinct patterns of insulin-like growth factor binding protein (IGFBP)-2 and IGFBP-3 expression in oxidant exposed lung epithelial cells. Biochim Biophys Acta: Mol Cell Res 2001, 1538:47-58.
58. Terrien X., Bonvin E., Corroyer S., Tabary O., Clement A., Henrion Caude A. Intracellular colocalization and interaction of IGF-binding protein-2 with the cyclin-dependent kinase inhibitor p21CIP1/WAF1 during growth inhibition. Biochem J 2005, 392:457-465. 10.1042/BJ20050517.
59. Miyako K., Cobb L.J., Francis M., Huang A., Peng B., Pintar J.E., et al. PAPA-1 is a nuclear binding partner of IGFBP-2 and modulates its growth-promoting actions. Mol Endocrinol 2009, 23:169-175.
60. Azar W.J., Azar S.H., Higgins S., Hu J.F., Hoffman A.R., Newgreen D.F., et al. IGFBP-2 enhances VEGF gene promoter activity and consequent promotion of angiogenesis by neuroblastoma cells. Endocrinology 2011, 152:3332-3342.
61. Azar W.J., Zivkovic S., Werther G.A., Russo V.C. IGFBP-2 nuclear translocation is mediated by a functional NLS sequence and is essential for its pro-tumorigenic actions in cancer cells. Oncogene 2014, 33:578-588.
62. Schedlich L.J., Le Page S.L., Firth S.M., Briggs L.J., Jans D.A., Baxter R.C. Nuclear import of insulin-like growth factor-binding protein-3 and -5 is mediated by the importin beta subunit. J Biol Chem 2000, 275(August (31)):23462-23470.
63. Iosef C., Gkourasas T., Jia C.Y., Li S.S., Han V.K. A functional nuclear localization signal in insulin-like growth factor binding protein-6 mediates its nuclear import. Endocrinology 2008, 149:1214-1226.
64. Chelsky D., Ralph R., Jonak G. Sequence requirements for synthetic peptide-mediated translocation to the nucleus. Mol Cell Biol 1989, 9:2487-2492.
65. Binkert C., Margot J.B., Landwehr J., Heinrich G., Schwander J. Structure of the human insulin-like growth factor binding protein-2 gene. Mol Endocrinol 1992, 6:826-836.
66. Werner H., Stannard B., Bach M.A., LeRoith D., Roberts C.T. Cloning and characterization of the proximal promoter region of the rat insulin-like growth factor I (IGF-I) receptor gene. Biochem Biophys Res Commun 1990, 169:1021-1027.
67. Brown A.L., Rechler M.M. Cloning of the rat insulin-like growth factor-binding protein-2 gene and identification of a functional promoter lacking a TATA box. Mol Endocrinol 1990, 4:2039-2051.
68. Boisclair Y.R., Brown A.L., Casola S., Rechler M.M. Three clustered Sp1 sites are required for efficient transcription of the TATA-less promoter of the gene for insulin-like growth factor-binding protein-2 from the rat. J Biol Chem 1993, 268:24892-24901.
69. Kwak I., Song S., Blum J.L., Simmen R.C., Simmen F.A. Enhancer- and silencer-like sequences that mediate insulin-like growth factor-binding protein-2 gene expression in uterine cells of pregnancy. DNA Cell Biol 2006, 25:6-18.
70. Cardona-Gomez G.P., Chowen J.A., Garcia-Segura L.M. Estradiol and progesterone regulate the expression of insulin-like growth factor-I receptor and insulin-like growth factor binding protein-2 in the hypothalamus of adult female rats. J Neurobiol 2000, 43:269-281.
71. Pons S., Torres-Aleman I. Estradiol modulates insulin-like growth factor I receptors and binding proteins in neurons from the hypothalamus. J Neuroendocrinol 1993, 5:267-271.
72. Badinga L., Song S., Simmen R.C., Simmen F.A. A distal regulatory region of the insulin-like growth factor binding protein-2 (IGFBP-2) gene interacts with the basic helix-loop-helix transcription factor, AP-4. Endocrine 1998, 8:281-289.
73. Kutoh E., Margot J., Schwander J. Cell-density (cycle) dependent silencer of the rat insulin-like growth factor binding protein-2 (IGFBP-2) gene. Growth Factors 1999, 16:217-223.
74. Cazals V., Nabeyrat E., Corroyer S., de Keyzer Y., Clement A. Role for NF-kappa B in mediating the effects of hyperoxia on IGF-binding protein 2 promoter activity in lung alveolar epithelial cells. Biochim Biophys Acta 1999, 1448:349-362.
75. Pintar J.E., Cerro J.A., Wood T.L. Genetic approaches to the function of insulin-like growth factor-binding proteins during rodent development. Horm Res 1996, 45:172-177. (Review, 60 refs).
76. Wood T.L., Rogler L.E., Czick M.E., Schuller A.G., Pintar J.E. Selective alterations in organ sizes in mice with a targeted disruption of the insulin-like growth factor binding protein-2 gene. Mol Endocrinol 2000, 14:1472-1482.
77. Chen T.L., Chang L.Y., DiGregorio D.A., Perlman A.J., Huang Y.F. Growth factor modulation of insulin-like growth factor-binding proteins in rat osteoblast-like cells. Endocrinology 1993, 133:1382-1389.
78. Palermo C., Manduca P., Gazzerro E., Foppiani L., Segat D., Barreca A. Potentiating role of IGFBP-2 on IGF-II-stimulated alkaline phosphatase activity in differentiating osteoblasts. Am J Physiol: Endocrinol Metab 2004, 286:E648-E657.
79. Wang E., Wang J., Chin E., Zhou J., Bondy C.A. Cellular patterns of insulin-like growth factor system gene expression in murine chondrogenesis and osteogenesis. Endocrinology 1995, 136:2741-2751.
80. Conover C.A., Johnstone E.W., Turner R.T., Evans G.L., John Ballard F., Doran P.M., et al. Subcutaneous administration of insulin-like growth factor (IGF)-II/IGF binding protein-2 complex stimulates bone formation and prevents loss of bone mineral density in a rat model of disuse osteoporosis. Growth Horm IGF Res 2002, 12:178-183.
81. Fisher M.C., Meyer C., Garber G., Dealy C.N. Role of IGFBP2. IGF-I and IGF-II in regulating long bone growth. Bone 2005, 37:741-750.
82. DeMambro V.E., Clemmons D.R., Horton L.G., Bouxsein M.L., Wood T.L., Beamer W.G., et al. Gender-specific changes in bone turnover and skeletal architecture in IGFBP-2-null mice. Endocrinology 2008, 149:2051-2061. 10.1210/en.2007-1068.
83. Kawai M., Breggia A.C., DeMambro V.E., Shen X., Canalis E., Bouxsein M.L., et al. The heparin-binding domain of IGFBP-2 has IGF binding-independent biologic activity in the growing skeleton. J Biol Chem 2011, 286(16):14670-14680.
84. Xi G., Wai C., DeMambro V., Rosen C.J., Clemmons D.R. IGFBP-2 directly stimulates osteoblast differentiation. J Bone Miner Res 2014, 29(11):2427-2438.
85. Hoeflich A., Wu M., Mohan S., Foll J., Wanke R., Froehlich T., et al. Overexpression of insulin-like growth factor-binding protein-2 in transgenic mice reduces postnatal body weight gain. Endocrinology 1999, 140:5488-5496.
86. Hoeflich A., Nedbal S., Blum W.F., Erhard M., Lahm H., Brem G., et al. Growth inhibition in giant growth hormone transgenic mice by overexpression of insulin-like growth factor-binding protein-2. Endocrinology 2001, 142:1889-1898.
87. Rehfeldt C., Renne U., Sawitzky M., Binder G., Hoeflich A. Increased fat mass, decreased myofiber size, and a shift to glycolytic muscle metabolism in adolescent male transgenic mice overexpressing IGFBP-2. Am J Physiol Endocrinol Metab 2010, 299:E287-E298.
88. Hoeflich A., Schmidt P., Foll J., Rottmann O., Weber M.M., Kolb H.J., et al. Altered growth of mice divergently selected for body weight is associated with complex changes in the growth hormone/insulin-like growth factor system. Growth Horm IGF Res 1998, 8:113-123.
89. Barrios V., Buno M., Pozo J., Munoz M.T., Argente J. Insulin-like growth factor-binding protein-2 levels in pediatric patients with growth hormone deficiency, eating disorders and acute lymphoblastic leukemia. Horm Res 2000, 53:221-227.
90. Hall K., Lundin G., Povoa G. Serum levels of the low molecular weight form of insulin-like growth factor binding protein in healthy subjects and patients with growth hormone deficiency, acromegaly and anorexia nervosa. Acta Endocrinol (Cph) 1988, 118:321-326.
91. Hotta M., Fukuda I., Sato K., Hizuka N., Shibasaki T., Takano K. The relationship between bone turnover and body weight, serum insulin-like growth factor (IGF) I, and serum IGF-binding protein levels in patients with anorexia nervosa. J Clin Endocrinol Metab 2000, 85:200-206.
92. Wheatcroft S.B., Kearney M.T., Shah A.M., Ezzat V.A., Miell J.R., Modo M., et al. IGF-binding protein-2 protects against the development of obesity and insulin resistance. Diabetes 2007, 56:285-294. 10.2337/db06-0436.
93. Hedbacker K., Birsoy K., Wysocki R.W., Asilmaz E., Ahima R.S., Farooqi I.S., et al. Antidiabetic effects of IGFBP2, a leptin-regulated gene. Cell Metab 2010, 11:11-22.
94. Claudio M., Benjamim F., Riccardo B., Massimiliano C., Francesco B., Luciano C. Adipocytes IGFBP-2 expression in prepubertal obese children. Obesity (Silver Spring) 2010, 18:2055-2057.
95. Ballerini M.G., Ropelato M.G., Domene H.M., Pennisi P., Heinrich J.J., Jasper H.G. Differential impact of simple childhood obesity on the components of the growth hormone-insulin-like growth factor (IGF)-IGF binding proteins axis. J Pediatr Endocrinol Metab 2004, 17:749-757.
96. Frystyk J., Skjaerbaek C., Vestbo E., Fisker S., Orskov H. Circulating levels of free insulin-like growth factors in obese subjects: the impact of type 2 diabetes. Diabetes Metab Res Rev 1999, 15:314-322.
97. Eckstein F., Pavicic T., Nedbal S., Schmidt C., Wehr U., Rambeck W., et al. Insulin-like growth factor-binding protein-2 (IGFBP-2) overexpression negatively regulates bone size and mass, but not density, in the absence and presence of growth hormone/IGF-I excess in transgenic mice. Anat Embryol (Berl) 2002, 206:139-148.
98. Diehl D., Hessel E., Oesterle D., Renner-Muller I., Elmlinger M., Langhammer M., et al. IGFBP-2 overexpression reduces the appearance of dysplastic aberrant crypt foci and inhibits growth of adenomas in chemically induced colorectal carcinogenesis. Int J Cancer 2009, 124:2220-2225.
99. Liou J.-M., Shun C.-T., Liang J.-T., Chiu H.-M., Chen M.-J., Chen C.C., et al. Plasma insulin-like growth factor-binding protein-2 levels as diagnostic and prognostic biomarker of colorectal cancer. J Clin Endocrinol Metab 2010, 95:1717-1720.
100. Levitt R.J., Georgescu M.-M., Pollak M. PTEN-induction in U251 glioma cells decreases the expression of insulin-like growth factor binding protein-2. Biochem Biophys Res Commun 2005, 336:1056-1061.
101. Mehrian-Shai R., Chen C.D., Shi T., Horvath S., Nelson S.F., Reichardt J.K., et al. Insulin growth factor-binding protein 2 is a candidate biomarker for PTEN status and PI3K/Akt pathway activation in glioblastoma and prostate cancer. Proc Natl Acad Sci U S A 2007, 104:5563-5568.
102. Martin J.L., Baxter R.C. Expression of insulin-like growth factor binding protein-2 by MCF-7 breast cancer cells is regulated through the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway. Endocrinology 2007, 148:2532-2541.
103. Dean S.J.R., Perks C.M., Holly J.M.P., Bhoo-Pathy N., Looi L.-M., Mohammed N.A.T., et al. Loss of PTEN expression is associated with IGFBP2 expression, younger age, and late stage in triple-negative breast cancer. Am J Clin Pathol 2014, 141:323-333.
104. Grimberg A., Coleman C.M., Shi Z., Burns T.F., MacLachlan T.K., Wang W., et al. Insulin-like growth factor binding protein-2 is a novel mediator of p53 inhibition of insulin-like growth factor signaling. Cancer Biol Ther 2006, 5:1408-1414.
105. Villani R.M., Adolphe C., Palmer J., Waters M.J., Wainwright B.J. Patched1 inhibits epidermal progenitor cell expansion and basal cell carcinoma formation by limiting Igfbp2 activity. Cancer Prev Res 2010, 3:1222-1234.
106. Rao G., Pedone C.A., Valle L.D., Reiss K., Holland E.C., Fults D.W. Sonic hedgehog and insulin-like growth factor signaling synergize to induce medulloblastoma formation from nestin-expressing neural progenitors in mice. Oncogene 2004, 23:6156-6162.
107. Feldser D., Agani F., Iyer N.V., Pak B., Ferreira G., Semenza G.L. Reciprocal positive regulation of hypoxia-inducible factor 1alpha and insulin-like growth factor 2. Cancer Res 1999, 59:3915-3918.
108. Harris A.L. Hypoxia - a key regulatory factor in tumour growth. Nat Rev Cancer 2002, 2:38-47.
109. 2 homeostasis by hypoxia-inducible factor 1. Annu Rev Cell Dev Biol 1999, 15:551-578.
110. Semenza G.L. Targeting HIF-1 for cancer therapy. Nat Rev Cancer 2003, 3:721-732.
111. Poomthavorn P., Wong S.H.X., Higgins S., Werther G.A., Russo V.C. Activation of a prometastatic gene expression program in hypoxic neuroblastoma cells. Endocr Relat Cancer 2009, 16:991-1004. 10.1677/ERC-08-0340.
112. Matsumoto T., Gargosky S.E., Iwasaki K., Rosenfeld R.G. Identification and characterization of insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs), and IGFBP proteases in human synovial fluid. J Clin Endocrinol Metab 1996, 81:150-155.
113. Ishikawa K., Ohe Y., Tatemoto K. Synthesis and secretion of insulin-like growth factor (IGF)-II and IGF binding protein-2 by cultivated brain meningeal cells. Brain Res 1995, 697:122-129.
114. Mark S., Kübler B., Höning S., Oesterreicher S., John H., Braulke T., et al. Diversity of human insulin-like growth factor (IGF) binding protein-2 fragments in plasma: primary structure. IGF-binding properties, and disulfide bonding pattern. Biochemistry 2005, 44:3644-3652.
115. Ho P.J., Baxter R.C. Characterization of truncated insulin-like growth factor-binding protein-2 in human milk. Endocrinology 1997, 138:3811-3818.
116. Pucilowska J.B., Davenport M.L., Kabir I., Clemmons D.R., Thissen J.P., Butler T., et al. The effect of dietary protein supplementation on insulin-like growth factors (IGFs) and IGF-binding proteins in children with shigellosis. J Clin Endocrinol Metab 1993, 77:1516-1521.
117. Brandt K., Lundell K., Brismar K. Neutrophil-derived azurocidin cleaves insulin-like growth factor-binding protein-1, -2 and -4. Growth Horm IGF Res 2011, 21:167-173.
118. DeGraff D.J., Malik M., Chen Q., Miyako K., Rejto L., Aguiar A.A., et al. Hormonal regulation of IGFBP-2 proteolysis is attenuated with progression to androgen insensitivity in the LNCaP progression model. J Cell Physiol 2007, 213:261-268.
119. Russo V.C., Andaloro E., Fornaro S.A., Najdovska S., Newgreen D.F., Bach L.A., et al. Fibroblast growth factor-2 over-rides insulin-like growth factor-I induced proliferation and cell survival in human neuroblastoma cells. J Cell Physiol 2004, 199:371-380.
120. Hoeflich A., Reisinger R., Schuett B.S., Elmlinger M.W., Russo V.C., Vargas G.A., et al. Peri/nuclear localization of intact insulin-like growth factor binding protein-2 and a distinct carboxyl-terminal IGFBP-2 fragment in vivo. Biochem Biophys Res Commun 2004, 324:705-710.
121. Si M., Nakamura M., Yano K., Ishii G., Hasebe T., Endoh Y., et al. Matrix metalloproteinase-7 triggers the matricrine action of insulin-like growth factor-II via proteinase activity on insulin-like growth factor binding protein 2 in the extracellular matrix. Cancer Sci 2007, 98:685-691.
122. Sunderic M., Miljus G., Nedic O. Interaction of insulin-like growth factor-binding protein 2 with alpha2-macroglobulin in the circulation. Protein J 2013, 32:138-142.
123. Gerard N., Delpuech T., Oxvig C., Overgaard M., Monget P. Proteolytic degradation of IGF-binding protein (IGFBP)-2 in equine ovarian follicles: involvement of pregnancy-associated plasma protein-A (PAPP-A) and association with dominant but not subordinated follicles. J Endocrinol 2004, 182:457-466.
124. Qin X., Wergedal J.E., Rehage M., Tran K., Newton J., Lam P., et al. Pregnancy-associated plasma protein-A increases osteoblast proliferation in vitro and bone formation in vivo. Endocrinology 2006, 147:5653-5661.
125. Ruoslahti E. RGD and other recognition sequences for integrins. Annu Rev Cell Dev Biol 1996, 12:697-715.
126. Schutt B., Langkamp M., Rauschnabel U., Ranke M., Elmlinger M. Integrin-mediated action of insulin-like growth factor binding protein-2 in tumor cells. J Mol Endocrinol 2004, 32:859-868. 10.1677/jme.0.0320859.
127. Mendes K.N., Wang G.K., Fuller G.N., Zhang W. JNK mediates insulin-like growth factor binding protein 2/integrin alpha5-dependent glioma cell migration. Int J Oncol 2010, 37:143-153.
128. Uzoh C.C., Holly J.M., Biernacka K.M., Persad R.A., Bahl A., Gillatt D., et al. Insulin-like growth factor-binding protein-2 promotes prostate cancer cell growth via IGF-dependent or -independent mechanisms and reduces the efficacy of docetaxel. Br J Cancer 2011, 104:1587-1593.
129. Arai T., Clarke J., Parker A., Busby W., Nam T., Clemmons D.R. Substitution of specific amino acids in insulin-like growth factor (IGF) binding protein 5 alters heparin binding and its change in affinity for IGF-I response to heparin. J Biol Chem 1996, 271:6099-6106.
130. Kiepe D., Van Der Pas A., Ciarmatori S., Standker L., Schutt B., Hoeflich A., et al. Defined carboxy-terminal fragments of insulin-like growth factor (IGF) binding protein-2 exert similar mitogenic activity on cultured rat growth plate chondrocytes as IGF-I. Endocrinology 2008, 149:4901-4911.
131. Xi G., Solum M.A., Wai C., Maile L.A., Rosen C.J., Clemmons D.R. The heparin-binding domains of IGFBP-2 mediate its inhibitory effect on preadipocyte differentiation and fat development in male mice. Endocrinology 2013, 154:4146-4157.
132. Seurin D., Lombet A., Babajko S., Godeau F., Ricort J.M. Insulin-like growth factor binding proteins increase intracellular calcium levels in two different cell lines. PLOS ONE 2013, 8:e59323.
133. Akl H., Bultynck G. Altered Ca++ signaling in cancer cells: proto-oncogenes and tumor suppressors targeting IP3 receptors. Biochim Biophys Acta: Rev Cancer 2013, 1835:180-193.
134. Rey O., Young S.H., Jacamo R., Moyer M.P., Rozengurt E. Extracellular calcium sensing receptor stimulation in human colonic epithelial cells induces intracellular calcium oscillations and proliferation inhibition. J Cell Physiol 2010, 225:73-83.
135. Young S.H., Rozengurt E. Crosstalk between insulin receptor and G protein-coupled receptor signaling systems leads to Ca(2+) oscillations in pancreatic cancer PANC-1 cells. Biochem Biophys Res Commun 2010, 401:154-158.
136. Ramadan J.W., Steiner S.R., O'Neill C.M., Nunemaker C.S. The central role of calcium in the effects of cytokines on beta-cell function: implications for type 1 and type 2 diabetes. Cell Calcium 2011, 50:481-490.
137. Shitara K., Yamada H., Watanabe K., Shimonaka M., Yamaguchi Y. Brain-specific receptor-type protein-tyrosine phosphatase RPTP beta is a chondroitin sulfate proteoglycan in vivo. J Biol Chem 1994, 269:20189-20193.
138. Schedlich L.J., O'Han M.K., Leong G.M., Baxter R.C. Insulin-like growth factor binding protein-3 prevents retinoid receptor heterodimerization: implications for retinoic acid-sensitivity in human breast cancer cells. Biochem Biophys Res Commun 2004, 314:83-88.
139. Schedlich L.J., Muthukaruppan A., O'Han M.K., Baxter R.C. Insulin-like growth factor binding protein-5 interacts with the vitamin D receptor and modulates the vitamin D response in osteoblasts. Mol Endocrinol 2007, 21:2378-2390. 10.1210/me.2006-0558.
140. Iosef C., Vilk G., Gkourasas T., Lee K.J., Chen B.P., Fu P., et al. Insulin-like growth factor binding protein-6 (IGFBP-6) interacts with DNA-end binding protein Ku80 to regulate cell fate. Cell Signal 2010, 22:1033-1043.
141. Liu B., Lee H.Y., Weinzimer S.A., Powell D.R., Clifford J.L., Kurie J.M., et al. Direct functional interactions between IGFBP-3 and RXR-α regulate transcriptional signalling and apoptosis. J Biol Chem 2000, 275(43):33607-33613.
142. Clemmons D.R., Snyder D.K., Busby W.H. Variables controlling the secretion of insulin-like growth factor binding protein-2 in normal human subjects. J Clin Endocrinol Metab 1991, 73:727-733.
143. Counts D.R., Gwirtsman H., Carlsson L.M., Lesem M., Cutler G.B. The effect of anorexia nervosa and refeeding on growth hormone-binding protein, the insulin-like growth factors (IGFs), and the IGF-binding proteins. J Clin Endocrinol Metab 1992, 75:762-767.
144. Berg U., Enqvist J.K., Mattsson C.M., Carlsson-Skwirut C., Sundberg C.J., Ekblom B., et al. Lack of sex differences in the IGF-IGFBP response to ultra endurance exercise. Scand J Med Sci Sports 2008, 18:706-714.
145. Gregory S.M., Spiering B.A., Alemany J.A., Tuckow A.P., Rarick K.R., Staab J.S., et al. Exercise-induced insulin-like growth factor I system concentrations after training in women. Med Sci Sports Exerc 2013, 45:420-428.
146. Chadan S.G., Dill R.P., Vanderhoek K., Parkhouse W.S. Influence of physical activity on plasma insulin-like growth factor-1 and insulin-like growth factor binding proteins in healthy older women. Mech Ageing Dev 1999, 109:21-34.
147. Nindl B.C., Kraemer W.J., Marx J.O., Arciero P.J., Dohi K., Kellogg M.D., et al. Overnight responses of the circulating IGF-I system after acute, heavy-resistance exercise. J Appl Physiol 2001, 90:1319-1326.
148. Eliakim A., Brasel J.A., Mohan S., Wong W.L.T., Cooper D.M. Increased physical activity and the growth hormone-IGF-I axis in adolescent males. Am J Physiol: Regul Integr Comp Physiol 1998, 275:R308-R314.
149. Deuschle M., Blum W.F., Frystyk J., Orskov H., Schweiger U., Weber B., et al. Endurance training and its effect upon the activity of the GH-IGFs system in the elderly. Int J Sports Med 1998, 19:250-254.
150. Kopple J.D., Cohen A.H., Wang H., Qing D., Tang Z., Fournier M., et al. Effect of exercise on mRNA levels for growth factors in skeletal muscle of hemodialysis patients. J Ren Nutr 2006, 16:312-324.
151. Riedl S., Kluge M., Schweitzer K., Waldhor T., Frisch H. Adaptation of ghrelin and the GH/IGF axis to high altitude. Eur J Endocrinol 2012, 166:969-976.
152. Beilharz E.J., Russo V.C., Butler G., Baker N.L., Connor B., Sirimanne E.S., et al. Co-ordinated and cellular specific induction of the components of the IGF/IGFBP axis in the rat brain following hypoxic-ischemic injury. Brain Res 1998, 59:119-134.
153. Sabin M.A., Russo V.C., Azar W.J., Yau S.W., Kiess W., Werther G.A. IGFBP-2 at the interface of growth and metabolism - implications for childhood obesity. Pediatr Endocrinol Rev 2011, 8:382-393.
154. Nam S.Y., Lee E.J., Kim K.R., Cha B.S., Song Y.D., Lim S.K., et al. Effect of obesity on total and free insulin-like growth factor (IGF)-1, and their relationship to IGF-binding protein (BP)-1, IGFBP-2, IGFBP-3, insulin, and growth hormone. Int J Obes Relat Metab Disord 1997, 21:355-359.
155. Heald A.H., Kaushal K., Siddals K.W., Rudenski A.S., Anderson S.G., Gibson J.M. Insulin-like growth factor binding protein-2 (IGFBP-2) is a marker for the metabolic syndrome. Exp Clin Endocrinol Diabetes 2006, 114:371-376.
156. Li Z., Picard F. Modulation of IGFBP2 mRNA expression in white adipose tissue upon aging and obesity. Horm Metab Res 2010, 42:787-791.
157. Krassas G.E. Endocrine abnormalities in anorexia nervosa. Pediatr Endocrinol Rev 2003, 1:46-54.
158. Allen N.E., Appleby P.N., Kaaks R., Rinaldi S., Davey G.K., Key T.J. Lifestyle determinants of serum insulin-like growth-factor-I (IGF-I), C-peptide and hormone binding protein levels in British women. Cancer Causes Control 2003, 14:65-74.
159. Li Z., Martin J., Poirier P., Caron-Cantin S.M., Hould F.S., Marceau S., et al. Upregulation of plasma insulin-like growth factor binding protein 2 levels after biliopancreatic diversion in humans. Obesity (Silver Spring) 2012, 20:1469-1473.
160. Wabitsch M., Blum W.F., Muche R., Heinze E., Haug C., Mayer H., et al. Insulin-like growth factors and their binding proteins before and after weight loss and their associations with hormonal and metabolic parameters in obese adolescent girls. Int J Obes Relat Metab Disord 1996, 20:1073-1080.
161. Bereket A., Lang C.H., Wilson T.A. Alterations in the growth hormone-insulin-like growth factor axis in insulin dependent diabetes mellitus. Horm Metab Res 1999, 31:172-181.
162. Frystyk J., Bek T., Flyvbjerg A., Skjærbæk C., Ørskov H. The relationship between the circulating IGF system and the presence of retinopathy in type 1 diabetic patients. Diabet Med 2003, 20:269-276.
163. Street M.E., Smerieri A., Montanini L., Predieri B., Iughetti L., Valenzise M., et al. Interactions among pro-inflammatory cytokines, IGF system and thyroid function in pre-pubertal obese subjects. J Biol Regul Homeost Agents 2013, 27:259-266.
164. Smerieri A., Petraroli M., Ziveri M.A., Volta C., Bernasconi S., Street M.E. Effects of cord serum insulin, IGF-II, IGFBP-2, IL-6 and cortisol concentrations on human birth weight and length: pilot study. PLoS ONE 2011, 6:e29562.
165. Giudice L.C., de Zegher F., Gargosky S.E., Dsupin B.A., de las Fuentes L., Crystal R.A., et al. Insulin-like growth factors and their binding proteins in the term and preterm human fetus and neonate with normal and extremes of intrauterine growth. J Clin Endocrinol Metab 1995, 80:1548-1555.
166. Ko J.M., Park H.K., Yang S., Hwang I.T. Influence of catch-up growth on IGFBP-2 levels and association between IGFBP-2 and cardiovascular risk factors in Korean children born SGA. Endocr J 2012, 59:725-733.
167. de Kort S.W., van Doorn J., van de Sande A.G., Leunissen R.W., Hokken-Koelega A.C. Serum insulin-like growth factor-binding protein-2 levels and metabolic and cardiovascular risk factors in young adults and children born small for gestational age. J Clin Endocrinol Metab 2010, 95:864-871.
168. Friedman J.M., Halaas J.L. Leptin and the regulation of body weight in mammals. Nature 1998, 395:763-770.
169. Yau S.W., Henry B.A., Russo V.C., McConell G.K., Clarke I.J., Werther G.A., et al. Leptin enhances insulin sensitivity by direct and sympathetic nervous system regulation of muscle IGFBP-2 expression - evidence from non-rodent models. Endocrinology 2014, 155(6):2133-2143.
170. Sabin M.A., Yau S.W., Russo V.C., Clarke I.J., Dunshea F.R., Chau J., et al. Dietary monounsaturated fat in early life regulates IGFBP2: implications for fat mass accretion and insulin sensitivity. Obesity 2011, 19:2374-2381.
171. Nam S., Lee E., Kim K., Cha B., Song Y., Lim S. Effect of obesity on total and free insulin-like growth factor (IGF)-1, and their relationship to IGF-binding protein (BP)-1, IGFBP-2, IGFBP-3, insulin, and growth hormone. Int J Obes Relat Metab Disord 1997, 21:355-359.
172. Ballerini M.G., Ropelato M.G., Domene H.M., Pennisi P., Heinrich J.J., Jasper H.G. Differential impact of simple childhood obesity on the components of the growth hormone-insulin-like growth factor (IGF)-IGF binding proteins axis. J Pediatr Endocrinol Metab 2004, 17:749-757.
173. Claudio M., Benjamim F., Riccardo B., Massimiliano C., Francesco B., Luciano C. Adipocytes IGFBP-2 expression in prepubertal obese children. Obesity 2010, 18:2055-2057.
174. Li Z., Picard F. Modulation of IGFBP2 mRNA expression in white adipose tissue upon aging and obesity. Horm Metab Res 2010, 42(11):787-791.
175. Wheatcroft S., Kearney M., Shah A., Ezzat V., Miell J., Modo M. IGF-binding protein-2 protects against the development of obesity and insulin resistance. Diabetes 2007, 56:284-294.
176. Yau S.W., Russo V.C., Clarke I.J., Dunshea F.R., Werther G.A., Sabin M.A. IGFBP-2 inhibits adipogenesis and lipogenesis in human visceral, but not subcutaneous, adipocytes. Int J Obes 2014, 10.1038/ijo.2014.192.
177. Reeve J.G., Kirby L.B., Brinkman A., Hughes S.A., Schwander J., Bleehen N.M. Insulin-like growth-factor-binding protein gene expression and protein production by human tumour cell lines. Int J Cancer 1992, 51:818-821.
178. Tennant M.K., Thrasher J.B., Twomey P.A., Birnbaum R.S., Plymate S.R. Insulin-like growth factor-binding protein-2 and -3 expression in benign human prostate epithelium, prostate intraepithelial neoplasia, and adenocarcinoma of the prostate. J Clin Endocrinol Metab 1996, 81:411-420.
179. Wex H., Vorwerk P., Mohnike K., Bretschneider D., Kluba U., Aumann V., et al. Elevated serum levels of IGFBP-2 found in children suffering from acute leukaemia is accompanied by the occurrence of IGFBP-2 mRNA in the tumour clone. Br J Cancer 1998, 78:515-520.
180. Ricard D., Idbaih A., Ducray F., Lahutte M., Hoang-Xuan K., Delattre J.-Y. Primary brain tumours in adults. Lancet 2012, 379:1984-1990.
181. Louis D.N., Ohgaki H., Wiestler O.D., Cavenee W.K., Burger P.C., Jouvet A., et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 2007, 114:97-109.
182. Fukushima T., Kataok A.H. Roles of insulin-like growth factor binding protein-2 (IGFBP-2) in glioblastoma. Anticancer Res 2007, 27:3685-3692.
183. Wang H., Shen W., Huang H., Hu L., Ramdas L., Zhou Y.H., et al. Insulin-like growth factor binding protein 2 enhances glioblastoma invasion by activating invasion-enhancing genes. Cancer Res 2003, 63:4315-4321.
184. Becher O.J., Peterson K.M., Khatua S., Santi M.R., MacDonald T.J. IGFBP2 is overexpressed by pediatric malignant astrocytomas and induces the repair enzyme DNA-PK. J Child Neurol 2008, 23:1205-1213.
185. Moore L.M., Holmes K.M., Smith S.M., Wu Y., Tchougounova E., Uhrbom L., et al. IGFBP2 is a candidate biomarker for Ink4a-Arf status and a therapeutic target for high-grade gliomas. Proc Natl Acad Sci U S A 2009, 106:16675-16679.
186. Elmlinger M.W., Deininger M.H., Schuett B.S., Meyermann R., Duffner F., Grote E.H., et al. In vivo expression of insulin-like growth factor-binding protein-2 in human gliomas increases with the tumor grade. Endocrinology 2001, 142:1652-1658.
187. Han S., Meng L., Han S., Wang Y., Wu A. Plasma IGFBP-2 levels after postoperative combined radiotherapy and chemotherapy predict prognosis in elderly glioblastoma patients. PLOS ONE 2014, 9:e93791.
188. Li Y., Jiang T., Zhang J., Zhang B., Yang W., You G., et al. Elevated serum antibodies against insulin-like growth factor-binding protein-2 allow detecting early-stage cancers: evidences from glioma and colorectal carcinoma studies. Ann Oncol 2012, 23:2415-2422.
189. Zheng S., Houseman E.A., Morrison Z., Wrensch M.R., Patoka J.S., Ramos C., et al. DNA hypermethylation profiles associated with glioma subtypes and EZH2 and IGFBP2 mRNA expression. Neuro Oncol 2011, 13:280-289.
190. Azar W.J., Werther G.A., Russo V.C. Dissecting the mechanisms of IGFBP-2 nuclear translocation in neuroblastoma cells. Endocr Rev 2011, 32:P1-P144.
191. Fukushima T., Tezuka T., Shimomura T., Nakano S., Kataoka H. Silencing of insulin-like growth factor-binding protein-2 in human glioblastoma cells reduces both invasiveness and expression of progression-associated gene CD24. J Biol Chem 2007, 282:18634-18644.
192. Wang G.K., Hu L., Fuller G.N., Zhang W. An interaction between insulin-like growth factor-binding protein 2 (IGFBP2) and integrin α5 is essential for IGFBP2-induced cell mobility. J Biol Chem 2006, 281:14085-14091.
193. Holmes K.M., Annala M., Chua C.Y., Dunlap S.M., Liu Y., Hugen N., et al. Insulin-like growth factor-binding protein 2-driven glioma progression is prevented by blocking a clinically significant integrin, integrin-linked kinase, and NF-kappaB network. Proc Natl Acad Sci U S A 2012, 109:3475-3480.
194. Heinlein C.A., Chang C. Androgen receptor in prostate cancer. Endocr Rev 2004, 25:276-308.
195. Karantanos T., Corn P.G., Thompson T.C. Prostate cancer progression after androgen deprivation therapy: mechanisms of castrate resistance and novel therapeutic approaches. Oncogene 2013, 32:5501-5511.
196. Kimura G., Kasuya J., Giannini S., Honda Y., Mohan S., Kawachi M., et al. Insulin-like growth factor (IGF) system components in human prostatic cancer cell-lines: LNCaP, DU145, and PC-3 cells. Int J Urol 1996, 3:39-46.
197. Cohen P., Peehl D.M., Stamey T.A., Wilson K.F., Clemmons D.R., Rosenfeld R.G. Elevated levels of insulin-like growth factor-binding protein-2 in the serum of prostate cancer patients. J Clin Endocrinol Metab 1993, 76:1031-1035.
198. Degraff D.J., Aguiar A.A., Sikes R.A. Disease evidence for IGFBP-2 as a key player in prostate cancer progression and development of osteosclerotic lesions. Am J Transl Res 2009, 1:115-130.
199. Wang H., Arun B.K., Wang H., Fuller G.N., Zhang W., Middleton L.P., et al. IGFBP2 and IGFBP5 overexpression correlates with the lymph node metastasis in T1 breast carcinomas. Breast J 2008, 14:261-267.
200. Juncker-Jensen A., Lykkesfeldt A.E., Worm J., Ralfkiær U., Espelund U., Jepsen J.S. Insulin-like growth factor binding protein 2 is a marker for antiestrogen resistant human breast cancer cell lines but is not a major growth regulator. Growth Horm IGF Res 2006, 16:224-239.
201. Sohn J., Do K.A., Liu S., Chen H., Mills G.B., Hortobagyi G.N., et al. Functional proteomics characterization of residual triple-negative breast cancer after standard neoadjuvant chemotherapy. Ann Oncol 2013, 24:2522-2526.
202. Mireuta M., Darnel A., Pollak M. IGFBP-2 expression in MCF-7 cells is regulated by the PI3K/AKT/mTOR pathway through Sp1-induced increase in transcription. Growth Factors 2010, 28:243-255.
203. Pollak M. Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer 2008, 8:915-928.
204. Mohanraj L., Oh Y. Targeting IGF-I, IGFBPs and IGF-I receptor system in cancer: the current and future in breast cancer therapy. Recent Pat Anticancer Drug Discov 2011, 6:166-177.
205. Valentinis B., Baserga R. IGF-I receptor signalling in transformation and differentiation. Mol Pathol 2001, 54:133-137.
206. Steuerman R., Shevah O., Laron Z. Congenital IGF1 deficiency tends to confer protection against post-natal development of malignancies. Eur J Endocrinol 2011, 164:485-489.
207. Moore T., Carbajal S., Beltran L., Perkins S.N., Yakar S., LeRoith D., et al. Reduced susceptibility to two-stage skin carcinogenesis in mice with low circulating insulin-like growth factor I levels. Cancer Res 2008, 68:3680-3688.
208. Jerome L., Shiry L., Leyland-Jones B. Deregulation of the IGF axis in cancer: epidemiological evidence and potential therapeutic interventions. Endocr Relat Cancer 2003, 10:561-578.
209. Pollak M. The insulin receptor/insulin-like growth factor receptor family as a therapeutic target in oncology. Clin Cancer Res 2012, 18:40-50.
210. Lee E.J., Mircean C., Shmulevich I., Wang H., Liu J., Niemisto A., et al. Insulin-like growth factor binding protein 2 promotes ovarian cancer cell invasion. Mol Cancer 2005, 4:7.
211. So A.I., Levitt R.J., Eigl B., Fazli L., Muramaki M., Leung S., et al. Insulin-like growth factor binding protein-2 is a novel therapeutic target associated with breast cancer. Clin Cancer Res 2008, 14:6944-6954.
212. Png K.J., Halberg N., Yoshida M., Tavazoie S.F. A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells. Nature 2012, 481:190-194.
213. Tombolan L., Orso F., Guzzardo V., Casara S., Zin A., Bonora M., et al. High IGFBP2 expression correlates with tumor severity in pediatric rhabdomyosarcoma. Am J Pathol 2011, 179:2611-2624.
214. Park K.H., Gad E., Goodell V., Dang Y., Wild T., Higgins D., et al. Insulin-like growth factor-binding protein-2 is a target for the immunomodulation of breast cancer. Cancer Res 2008, 68:8400-8409.
215. Piura E., Piura B. Autoantibodies to tumor-associated antigens in breast carcinoma. J Oncol 2010, 2010. Article ID 264926, 14 pages.
216. Disis M.L., Gad E., Herendeen D.R., Lai V.P., Park K.H., Cecil D.L., et al. A multiantigen vaccine targeting Neu, IGFBP-2, and IGF-IR prevents tumor progression in mice with preinvasive breast disease. Cancer Prev Res 2013, 6:1273-1282.
217. Heidegger I., Pircher A., Klocker H., Massoner P. Targeting the insulin-like growth factor network in cancer therapy. Cancer Biol Ther 2011, 11:701-707.
218. Soh C.L., McNeil K., Owczarek C.M., Hardy M.P., Fabri L.J., Pearse M., et al. Exogenous administration of protease-resistant, non-matrix-binding IGFBP-2 inhibits tumour growth in a murine model of breast cancer. Br J Cancer 2014, 110(12):2855-2864.