Abstract 1503: Cancer testis antigen SPANXB2 and prostate cancer progression: Human prostate stroma promotes SPANXB2 expression

A critical problem in prostate cancer is our inability to reliably distinguish indolent from aggressive disease. Recent evidence has implicated a class of genes, termed Cancer Testis Antigens (CTA) that uniquely expressed on malignant tissue, in cancer progression. CTA SPANXB2 was reported to be associated with aggressive and metastasis of melanoma and other cancers. The role of SPANXB2 in prostate cancer is still uncertain. In preliminary studies, we observed that the CTA SPANXB2 is up-regulated in mRNA level in metastatic prostate cancer xenograft models (PC3 cells injected in mouse dorsal prostate with Matrigel). Compared with other injection sites, mouse dorsal prostate enriched prostate stroma. Therefore, we further tested whether prostate stroma is the key factor to influence SPANXB2 expression and enhance the metastasis potential of prostate cancer cells. We validated this through an in vitro epithelial-stroma interaction models: GFP labeled PC3 cells were placed on the top of human prostate stromal cells (HPS-19I); two days later PC3-GFP cells were isolated through flow cytometry with high purity (> 99%). By real time PCR, the expression level of SPANXB2 in these purified PC3-GFP cells was found to be upregulated up to 10 folds. We also tested DU145 and LNCaP in this same model, and similar results were obtained. We further examined the migration and invasion ability of these cells and found that stromal exposed cells gained an enhanced ability to migrate and invade. Interestingly, we also observed that the stem cells marker, CD24 was highly up -regulated up to 6 folds in PC3 cells after co-culture with HPS-19I. In addition, we treated PC3 cells with TGF-β1 and TGF-β2, and noted that SPANXB2 and CD24 were significantly increased in PC3 cells after 24 hours treatment with TGF-β2. Our results reveal that i) the interaction between human prostate stromal cells and prostate cancer cells promote CTA-SPANXB2 and CD24 expression in prostate cancer cells, ii) these interactions further enhance the migration and invasion ability of prostate cancer cells and iii) TGF-β2 may regulate SPANXB expression relevant cells. These data provide rationale for studying SPANXB2 in stromal-epithelial interactions and may be potentially used to pinpoint druggable targets that drive metastasis and that distinguish indolent from aggressive prostate cancer. Keywords: Cancer testis antigen, SPANXB2, Prostate cancer, Metastasis, Stoma Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1503. doi:1538-7445.AM2012-1503