VCAM1 Expression Correlated with Tumorigenesis, Chemoresistance and Poor Prognosis in High Grade Serous Ovarian Cancer
Jianfei Huang, Jing Zhang, Weiwei Shan, Imelda Mercado-Uribe, Jinsong Liu. MD Anderson Cancer Center of Texas University, Houston, TX; Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
Background: High expression of vascular cell adhesion molecule 1 (VCAM1) has been shown to be associated with several cancers although its function in cancer development is largely undefined. Our previous studied demonstrated that VCAM1 expression is increased in RAS-transformed ovarian epithelial cells. The purpose of this study is to investigate its role in ovarian cancer using RAS-transformed ovarian epithelial cells and ovarian cancer cell lines and correlate its expression with clinical pathologic parameters in a cohort of ovarian cancer patients.
Design: We examined the expression of VCAM1 by immunohistochemical staining in 251 high grade serous carcinoma using ovarian cancer tissue microarray. The expression of VCAM1 was silenced in RAS-transformed ovarian epithelial cell lines and three high grade ovarian cancer cell lines (OVCA433, OVCA429, and SKOV3) using retrovirus-mediated silencing. Cell proliferation, colony formation, and migration, and chemosensitivity assay were analyzed in vitro and effect on tumor growth was analyzed in nude mice.
Results: High VCAM1 expression in cancer cells was related with response to treat with surgery and chemical drugs (P = 0.025) and elder age at diagnosis (P = 0.008). Cox regression univariate and multivariable analysis showed that VCAM1 expression in tumor cells was an independent prognostic factor. Ovarian cancer cells with VCAM1 overexpression, compared with corresponding control cells, had increased cell proliferation, colony formation, migration, chemoresistance, and enhanced growth of xenograft tumors in mice, especially the tumor cells maintained with fibroblast cells with high VCAM1 expression.
Conclusions: VCAM1 plays an important role in promoting tumor growth of ovarian cancer. It may be used as a prognostic factor and novel therapeutic target for ovarian cancer.
Category: Gynecologic & Obstetrics
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 188, Wednesday Morning