Insulin-like Growth Factor Binding Protein 2 Promotes Ovarian Cancer Cell Invasion

Overview

Journal Mol Cancer

Publisher Biomed Central

Specialties Molecular Biology
Oncology

Date 2005 Feb 3

PMID 15686601

Citations 40

Authors

Eun-Ju Lee

Cristian Mircean

Ilya Shmulevich

Huamin Wang

Jinsong Liu

Antti Niemisto

John J Kavanagh

Je-Ho Lee

Wei Zhang

Affiliations

Soon will be listed here.

Abstract

Background: Insulin-like growth factor binding protein 2 (IGFBP2) is overexpressed in ovarian malignant tissues and in the serum and cystic fluid of ovarian cancer patients, suggesting an important role of IGFBP2 in the biology of ovarian cancer. The purpose of this study was to assess the role of increased IGFBP2 in ovarian cancer cells.

Results: Using western blotting and tissue microarray analyses, we showed that IGFBP2 was frequently overexpressed in ovarian carcinomas compared with normal ovarian tissues. Furthermore, IGFBP2 was significantly overexpressed in invasive serous ovarian carcinomas compared with borderline serous ovarian tumors. To test whether increased IGFBP2 contributes to the highly invasive nature of ovarian cancer cells, we generated IGFBP2-overexpressing cells from an SKOV3 ovarian cancer cell line, which has a very low level of endogenous IGFBP2. A Matrigel invasion assay showed that these IGFBP2-overexpressing cells were more invasive than the control cells. We then designed small interference RNA (siRNA) molecules that attenuated IGFBP2 expression in PA-1 ovarian cancer cells, which have a high level of endogenous IGFBP2. The Matrigel invasion assay showed that the attenuation of IGFBP2 expression indeed decreased the invasiveness of PA-1 cells.

Conclusions: We therefore showed that IGFBP2 enhances the invasion capacity of ovarian cancer cells. Blockage of IGFBP2 may thus constitute a viable strategy for targeted cancer therapy.

Citing Articles

Regulates the Proliferation and Apoptosis of Ovarian Granulosa Cells by Targeting in Zhedong White Geese.

Wang S, Zeng C, Pan Y, Zang Z, Zhang Y, Yue S Animals (Basel). 2025; 15(5).

PMID: 40075946 PMC: 11898151. DOI: 10.3390/ani15050663.

Reprogramming of normal fibroblasts into ovarian cancer-associated fibroblasts via non-vesicular paracrine signaling induces an activated fibroblast phenotype.

Axemaker H, Plesselova S, Calar K, Jorgensen M, Wollman J, de la Puente P Biochim Biophys Acta Mol Cell Res. 2024; 1871(7):119801.

PMID: 39038611 PMC: 11365755. DOI: 10.1016/j.bbamcr.2024.119801.

Quantification of putative ovarian cancer serum protein biomarkers using a multiplexed targeted mass spectrometry assay.

Ryu J, Boylan K, Twigg C, Evans R, Skubitz A, Thomas S Clin Proteomics. 2024; 21(1):1.

PMID: 38172678 PMC: 10762856. DOI: 10.1186/s12014-023-09447-4.

The "Sweet Spot" of Targeting Tumor Metabolism in Ovarian Cancers.

Tondo-Steele K, McLean K Cancers (Basel). 2022; 14(19).

PMID: 36230617 PMC: 9562887. DOI: 10.3390/cancers14194696.

Spatial Transcriptomic Analysis of Ovarian Cancer Precursors Reveals Reactivation of IGFBP2 during Pathogenesis.

Wang Y, Huang P, Wang B, Murdock T, Cope L, Hsu F Cancer Res. 2022; 82(24):4528-4541.

PMID: 36206311 PMC: 9808976. DOI: 10.1158/0008-5472.CAN-22-1620.

References

Lang J . Lymph node metastasis in stage I ovarian carcinoma. Chin Med J (Engl). 1994; 107(9):643-7. View

Richardsen E, Ukkonen T, Bjornsen T, Mortensen E, Egevad L, Busch C . Overexpression of IGBFB2 is a marker for malignant transformation in prostate epithelium. Virchows Arch. 2003; 442(4):329-35. DOI: 10.1007/s00428-003-0786-2. View

Rosen D, Huang X, Deavers M, Malpica A, Silva E, Liu J . Validation of tissue microarray technology in ovarian carcinoma. Mod Pathol. 2004; 17(7):790-7. DOI: 10.1038/modpathol.3800120. View

Zumkeller W, Schwander J, Mitchell C, Morrell D, Schofield P, Preece M . Insulin-like growth factor (IGF)-I, -II and IGF binding protein-2 (IGFBP-2) in the plasma of children with Wilms' tumour. Eur J Cancer. 1993; 29A(14):1973-7. DOI: 10.1016/0959-8049(93)90455-o. View

Akmal S, Yun K, Maclay J, Higami Y, Ikeda T . Insulin-like growth factor 2 and insulin-like growth factor binding protein 2 expression in hepatoblastoma. Hum Pathol. 1995; 26(8):846-51. DOI: 10.1016/0046-8177(95)90005-5. View

Elmlinger M, Deininger M, Schuett B, Meyermann R, Duffner F, Grote E . In vivo expression of insulin-like growth factor-binding protein-2 in human gliomas increases with the tumor grade. Endocrinology. 2001; 142(4):1652-8. DOI: 10.1210/endo.142.4.8084. View

Flyvbjerg A, Mogensen O, Mogensen B, Nielsen O . 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. 1997; 82(7):2308-13. DOI: 10.1210/jcem.82.7.4085. View

Babajko S, Grellier P, de Galle B, Menouny M, BINOUX M . IGFBPs are involved in xenograft development in nude mice. Med Pediatr Oncol. 2001; 36(1):154-6. DOI: 10.1002/1096-911X(20010101)36:1<154::AID-MPO1037>3.0.CO;2-L. View

Mita K, Nakahara M, Usui T . Expression of the insulin-like growth factor system and cancer progression in hormone-treated prostate cancer patients. Int J Urol. 2000; 7(9):321-9. DOI: 10.1046/j.1442-2042.2000.00200.x. View

10.

Tennant M, Thrasher J, Twomey P, Birnbaum R, Plymate S . 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(1):411-20. DOI: 10.1210/jcem.81.1.8550786. View

11.

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(3):859-68. DOI: 10.1677/jme.0.0320859. View

12.

Godard S, Getz G, Delorenzi M, Farmer P, Kobayashi H, Desbaillets I . Classification of human astrocytic gliomas on the basis of gene expression: a correlated group of genes with angiogenic activity emerges as a strong predictor of subtypes. Cancer Res. 2003; 63(20):6613-25. View

13.

Julian C, Woodruff J . The biologic behavior of low-grade papillary serous carcinoma of the ovary. Obstet Gynecol. 1972; 40(6):860-7. View

14.

Karasik A, Menczer J, Pariente C, Kanety H . Insulin-like growth factor-I (IGF-I) and IGF-binding protein-2 are increased in cyst fluids of epithelial ovarian cancer. J Clin Endocrinol Metab. 1994; 78(2):271-6. DOI: 10.1210/jcem.78.2.7508947. View

15.

Kanety H, Kattan M, Goldberg I, Kopolovic J, Ravia J, Menczer J . Increased insulin-like growth factor binding protein-2 (IGFBP-2) gene expression and protein production lead to high IGFBP-2 content in malignant ovarian cyst fluid. Br J Cancer. 1996; 73(9):1069-73. PMC: 2074413. DOI: 10.1038/bjc.1996.206. View

16.

Lancaster J, Dressman H, Whitaker R, Havrilesky L, Gray J, Marks J . Gene expression patterns that characterize advanced stage serous ovarian cancers. J Soc Gynecol Investig. 2004; 11(1):51-9. DOI: 10.1016/j.jsgi.2003.07.004. View

17.

Morice P, Joulie F, Camatte S, Atallah D, Rouzier R, Pautier P . Lymph node involvement in epithelial ovarian cancer: analysis of 276 pelvic and paraaortic lymphadenectomies and surgical implications. J Am Coll Surg. 2003; 197(2):198-205. DOI: 10.1016/S1072-7515(03)00234-5. View

18.

Mishra L, Bass B, Ooi B, Sidawy A, Korman L . Role of insulin-like growth factor-I (IGF-I) receptor, IGF-I, and IGF binding protein-2 in human colorectal cancers. Growth Horm IGF Res. 2000; 8(6):473-9. DOI: 10.1016/s1096-6374(98)80300-6. View

19.

Moore M, Wetterau L, Francis M, Peehl D, Cohen P . Novel stimulatory role for insulin-like growth factor binding protein-2 in prostate cancer cells. Int J Cancer. 2003; 105(1):14-9. DOI: 10.1002/ijc.11015. View

20.

Niemisto A, Hu L, Yli-Harja O, Zhang W, Shmulevich I . Quantification of in vitro cell invasion through image analysis. Conf Proc IEEE Eng Med Biol Soc. 2007; 2004:1703-6. DOI: 10.1109/IEMBS.2004.1403512. View