Basigin-2 is the predominant basigin isoform that promotes tumor cell migration and invasion and correlates with poor pr

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Basigin-2 is the predominant basigin isoform that promotes tumor cell migration and invasion and correlates with poor prognosis in epithelial ovarian cancer Shu-Hua Zhao1†, Yu Wang2†, Li Wen3†, Zhen-Bo Zhai4, Zhen-Hua Ai2, Nian-Ling Yao1, Li Wang5, Wen-Chao Liu2, Bi-Liang Chen1, Yu Li5* and Hong Yang1*

Abstract Background: Basigin, which has four isoforms, has been demonstrated to be involved in progression of various human cancers. The aim of this study was to examine the prognostic value of basigin-2 protein expression in epithelial ovarian cancer. Furthermore, the function of basigin-2 in ovarian cancer was further investigated in cell culture models. Methods: Immunohistochemistry staining was performed to investigate basigin-2 expression in a total of 146 ovarian tissue specimens. Kaplan Meier analysis and Cox proportional hazards model were applied to assess the relationship between basigin-2 and progression-free survival (PFS) and overall survival (OS). Real-time PCR, RT-PCR and western blot were used to explore basigin-2, basigin-3 and basigin-4 expression in ovarian cancer cell lines and tissues. To evaluate possible contributions of basigin-2 to MMP secretion and cell migration and invasion, the overexpression vectors pcDNA3.1-basigin-2 and basigin-2 siRNA were transfected into HO-8910 and HO-8910 PM cells respectively. Results: High basigin-2 expression was associated with lymph-vascular space involvement, lymph node metastasis and poor prognosis of epithelial ovarian cancer. Multivariate analyses indicated that basigin-2 positivity was an independent prognostic factor for PFS (P = 0.006) and OS (P = 0.019), respectively. Overexpression of basigin-2 increased the secretion of MMP-2/9 and cancer cell migration and invasion of HO-8910 cells, whereas knockdown of basigin-2 reduced active MMP-2/9 production, migration and invasion of HO-8910 PM cells. Conclusions: The expression of basigin-2 might be an independent prognostic marker and basigin-2 inhibition would be a potential strategy for epithelial ovarian cancer patients, especially in inhibiting and preventing cancer cell invasion and metastasis. Keywords: Ovarian cancer, Basigin-2, Prognosis, Survival, Migration, Invasion

* Correspondence: [email protected]; [email protected] † Equal contributors 5 Cell Engineering Research Centre and Department of Cell Biology, State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi’an 710032, China 1 Department of Obstetrics and Gynecology, Xijing Hospital, The Fourth Military Medical University, Xi’an 710032, China Full list of author information is available at the end of the article © 2013 Zhao et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Zhao et al. Journal of Translational Medicine 2013, 11:92 ht