Abstract 410: Expression of class 3 semaphorins in prostate cancer and modulation by hypoxia

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Class 3 semaphorins are secreted proteins that act as guidance cues for migrating cells via their transmembrane receptors, plexins. Semaphorins have a role in cancer affecting tumour growth both directly and indirectly, by affecting angiogenesis. The aims of this study were to determine if semaphorins have a potential role in prostate cancer and if their expression is regulated by hypoxia. Here we show that semaphorins and their transmembrane receptors, plexins and neuropilins, are widely expressed in prostate cancer cell lines and tissue with a significant overexpression of Sema3E in tumour tissue. Co-expression of semaphorins and their receptors by tumour cells suggests that semaphorins may act through an autocrine or paracrine mechanism in prostate cancer cells and have a direct effect on prostate tumour progression. We found that Sema3E affected integrin-mediated adhesion to fibronectin of prostate cancer cells, either enhancing or inhibiting adhesion, depending on cellular context. Sema3E also inhibited the migration of prostate cancer cells. As well as affecting tumour progression directly, class 3 semaphorins act as angiogenesis factors. We found that expression of several semaphorin genes is affected by growth in hypoxic conditions. Notably, expression of sema3C is upregulated and Sema3A and Sema3E are down regulated by hypoxia in prostate and colon cancer cells. The down-regulation of sema3A and 3E by hypoxia is consistent with a role for Sema3A and 3E as anti-angiogenic factors in prostate cancer. These results indicate a potential role for Sema3E in prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 410.