Insulin-like growth factor binding protein 2 promotes ovarian cancer cell invasion.
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.
Lee
Eun-Ju
EJ
Department of Pathology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, Texas, 77030, USA. lej1943@yahoo.com
Mircean
Cristian
C
Shmulevich
Ilya
I
Wang
Huamin
H
Liu
Jinsong
J
Niemistö
Antti
A
Kavanagh
John J
JJ
Lee
Je-Ho
JH
Zhang
Wei
W
D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism
D018971:Insulin-Like Growth Factor Binding Protein 2; D034741:RNA, Small Interfering