Journal of Clinical Endocrinology & Metabolism, Vol 78, 271-276, Copyright © 1994 by Endocrine Society

ARTICLES

Insulin-like growth factor-I (IGF-I) and IGF-binding protein-2 are increased in cyst fluids of epithelial ovarian cancer

A Karasik, J Menczer, C Pariente and H Kanety
Institute of Endocrinology, Chaim Sheba Medical Center, Tel-Hashomer, Israel.

Expression of insulin-like growth factor-I (IGF-I), its receptor, and IGF-binding proteins (IGFBPs) by epithelial ovarian cancer cells and its mitogenic effect on these cells in vitro suggest that IGF-I may have a role in the regulation of human ovarian cancer. To examine this role in vivo, we explored the IGF-I/IGFBP system in sera and cyst fluids of women undergoing surgery for simple and other benign cysts (n = 20) and borderline (n = 5) and invasive malignant epithelial neoplasms (n = 11). The IGF-I level was significantly higher in cyst fluid from invasive malignant compared to cyst fluid in benign neoplasms (16.1 +/- 2.2 vs. 7.3 +/- 1.2 nmol/L; P = 0.002). Although benign cysts contained almost no IGFBP, high IGFBP-2 levels were detected in malignant cysts regardless of histological type. Serum IGFBP-2 levels were also higher in women with invasive malignancy than in benign controls (1.32 +/- 0.32 vs. 0.53 +/- 0.07 relative units; P = 0.004). IGFBP-2 was higher in cyst fluids than in the corresponding sera, implying local production of this protein. Estradiol was high in fluid from invasive malignant cysts of postmenopausal women and correlated with IGF-I in the cyst fluid. Levels of IGF-I, IGFBP-2, and estradiol in cyst fluid could discriminate between benign and malignant neoplasms, except for the endometrioid-type tumors (n = 2). Our data support a role for IGF-I in the proliferation of ovarian cancer and suggest that IGF-I and estradiol interact in regulating this malignancy.

This article has been cited by other articles:

				S. S. Tworoger, I-M. Lee, J. E. Buring, M. N. Pollak, and S. E. Hankinson Insulin-like Growth Factors and Ovarian Cancer Risk: A Nested Case-Control Study in Three Cohorts Cancer Epidemiol. Biomarkers Prev., August 1, 2007; 16(8): 1691 - 1695. [Abstract] [Full Text] [PDF]

				J. L. Martin and R. C. Baxter 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, May 1, 2007; 148(5): 2532 - 2541. [Abstract] [Full Text] [PDF]

				J. L. Eiseman, J. Guo, R. K. Ramanathan, C. P. Belani, D. B. Solit, H. I. Scher, S. P. Ivy, E. G. Zuhowski, and M. J. Egorin Evaluation of Plasma Insulin-like Growth Factor Binding Protein 2 and Her-2 Extracellular Domain as Biomarkers for 17-Allylamino-17-Demethoxygeldanamycin Treatment of Adult Patients with Advanced Solid Tumors Clin. Cancer Res., April 1, 2007; 13(7): 2121 - 2127. [Abstract] [Full Text] [PDF]

				S. M. Firth and R. C. Baxter Cellular Actions of the Insulin-Like Growth Factor Binding Proteins Endocr. Rev., December 1, 2002; 23(6): 824 - 854. [Abstract] [Full Text] [PDF]

				J. A. Arraztoa, P. Monget, C. Bondy, and J. Zhou Expression Patterns of Insulin-Like Growth Factor-Binding Proteins 1, 2, 3, 5, and 6 in the Mid-Cycle Monkey Ovary J. Clin. Endocrinol. Metab., November 1, 2002; 87(11): 5220 - 5228. [Abstract] [Full Text] [PDF]

				K. Ong, J. Kratzsch, W. Kiess, and D. Dunger Circulating IGF-I Levels in Childhood Are Related to Both Current Body Composition and Early Postnatal Growth Rate J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1041 - 1044. [Abstract] [Full Text] [PDF]

				S. F. Shariat, D. J. Lamb, M. W. Kattan, C. Nguyen, J. Kim, J. Beck, T. M. Wheeler, and K. M. Slawin Association of Preoperative Plasma Levels of Insulin-Like Growth Factor I and Insulin-Like Growth Factor Binding Proteins-2 and -3 With Prostate Cancer Invasion, Progression, and Metastasis J. Clin. Oncol., February 1, 2002; 20(3): 833 - 841. [Abstract] [Full Text] [PDF]

				A. Hoeflich, R. Reisinger, H. Lahm, W. Kiess, W. F. Blum, H. J. Kolb, M. M. Weber, and E. Wolf Insulin-like Growth Factor-binding Protein 2 in Tumorigenesis: Protector or Promoter? Cancer Res., December 1, 2001; 61(24): 8601 - 8610. [Full Text] [PDF]

				W Zumkeller IGFs and IGFBPs: surrogate markers for diagnosis and surveillance of tumour growth? Mol. Pathol., October 1, 2001; 54(5): 285 - 288. [Abstract] [Full Text] [PDF]

				N. Auersperg, A. S. T. Wong, K.-C. Choi, S. K. Kang, and P. C. K. Leung Ovarian Surface Epithelium: Biology, Endocrinology, and Pathology Endocr. Rev., April 1, 2001; 22(2): 255 - 288. [Abstract] [Full Text]

				H. Yu and T. Rohan Role of the Insulin-Like Growth Factor Family in Cancer Development and Progression J Natl Cancer Inst, September 20, 2000; 92(18): 1472 - 1489. [Abstract] [Full Text] [PDF]

				H. M. Khandwala, I. E. McCutcheon, A. Flyvbjerg, and K. E. Friend The Effects of Insulin-Like Growth Factors on Tumorigenesis and Neoplastic Growth Endocr. Rev., June 1, 2000; 21(3): 215 - 244. [Abstract] [Full Text]

				G. N. Fuller, C. H. Rhee, K. R. Hess, L. S. Caskey, R. Wang, J. M. Bruner, W. K. A. Yung, and W. Zhang Reactivation of Insulin-like Growth Factor Binding Protein 2 Expression in Glioblastoma Multiforme: A Revelation by Parallel Gene Expression Profiling Cancer Res., September 1, 1999; 59(17): 4228 - 4232. [Abstract] [Full Text] [PDF]

				D. Coppola, B. Saunders, L. Fu, W. Mao, and S. V. Nicosia The Insulin-like Growth Factor 1 Receptor Induces Transformation and Tumorigenicity of Ovarian Mesothelial Cells and Down-Regulates Their Fas-Receptor Expression Cancer Res., July 1, 1999; 59(13): 3264 - 3270. [Abstract] [Full Text] [PDF]

				N. Boulle, A. Logié, C. Gicquel, L. Perin, and Y. Le Bouc Increased Levels of Insulin-Like Growth Factor II (IGF-II) and IGF-Binding Protein-2 Are Associated with Malignancy in Sporadic Adrenocortical Tumors J. Clin. Endocrinol. Metab., May 1, 1998; 83(5): 1713 - 1720. [Abstract] [Full Text]

				A. Flyvbjerg, O. Mogensen, B. Mogensen, and O. S. Nielsen Elevated Serum Insulin-Like Growth Factor-Binding Protein 2 (IGFBP-2) and Decreased IGFBP-3 in Epithelial Ovarian Cancer: Correlation with Cancer Antigen 125 and Tumor-Associated Trypsin Inhibitor J. Clin. Endocrinol. Metab., July 1, 1997; 82(7): 2308 - 2313. [Abstract] [Full Text] [PDF]