Insulin-like growth factor binding protein 2 promotes ovarian cancer cell invasion

Eun-Ju Lee,John J Kavanagh,Ilya Shmulevich,Jinsong Liu,Je-Ho Lee,Antti Niemistö,Huamin Wang,Cristian Mircean,Wei Zhang

doi:10.1186/1476-4598-4-7

Abstract

BackgroundInsulin-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.ResultsUsing 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.ConclusionsWe 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.

Highlights

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
IGFBP2 is associated with invasive epithelial ovarian carcinoma We first performed western blotting analysis using frozen tissue specimens, which consisted of four paired normal and carcinomatous ovarian tissues, one normal ovarian tissue, and three unpaired ovarian carcinoma tissues
We compared the expression of IGFBP2 in normal ovaries, borderline serous ovarian tumors, and invasive serous ovarian carcinomas using a tissue microarray, which showed that IGFBP2 was expressed at significantly different levels between normal tissues and borderline tumors (p = 0.03) and between borderline tumors and invasive carcinomas (p = 0.03) (Figure 1B, Table 1)

Summary

Introduction

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. Molecular Cancer 2005, 4:7 http://www.molecular-cancer.com/content/4/1/7 the fact that the molecular events responsible for the biological behavior of ovarian cancer are poorly understood Implicated in both ovarian tumorigenesis and physiological follicular proliferation are the insulin-like growth factor I (IGF-I) and IGF-II systems. The progression-free interval and overall survival have proved to be significantly shorter in patients with a high serum level of IGFBP2 at diagnosis than in those with lower levels [6] Taken together, these data suggest an important role for IGFBP2 in the biology of ovarian cancer

Objectives

Methods

Results

Conclusion