Abstract 5331: The effect of heat shock protein 27 (HSP27) on prostate cancer cell adhesion, invasion and metastasis

Abstract

Abstract Prostate cancer (PCa) is the most commonly diagnosed form of cancer among American men, and the second leading cause of all cancer-related deaths. PCa death is caused by the process of metastasis. In order to metastasize, tumor cells must acquire a series of phenotypic alterations, collectively known as the metastatic cascade. We have demonstrated that the small heat-shock protein, HSP27, affects key early steps of the metastatic cascade, and therefore may be a regulator of human PCa metastasis. HSP27 protein expression increases during PCa progression. It is phosphorylated in response to signaling from transforming growth factor-β (TGF-β), which in turn increases matrix metalloproteinase 2 (MMP-2) and cell invasion in vitro. We now demonstrate that HSP27 does not affect human PCa cell adhesion, cell detachment or cell migration, all of which contribute to the composite function of cell invasion. We went on to show that proteolysis by MMPs is necessary for HSP27-driven cell invasion by demonstrating that it was abrogated Marimastat, a broad-spectrum MMP inhibitor. By orthotopically implanting HSP27 variant human PCa cell lines, we demonstrated that HSP27 increases metastasis in a murine model. We also found that HSP27 increased tumor size. HSP27 increases human PCa metastasis and tumor growth in vivo. These findings provide a mechanistic explanation for the poor prognosis associated with increased HSP27 expression in human prostate tissue. 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 5331. doi:1538-7445.AM2012-5331