The role of Heat Shock Protein 27 (HSP27) in the metastatic progression of human prostate cancer

Prostate cancer (PCa) is the most common form of cancer in American men. Mortality from PCa is caused by the movement of cancer cells from the primary organ to distant sites, where they grow to become metastatic tumors. Heat shock protein 27 (HSP27) is an actin-capping protein that is increasingly overexpressed during PCa progression in humans. The role of HSP27 in driving PCa cell movement from the prostate gland to distant metastatic sites is unknown. We hypothesized that HSP27 will increase human PCa metastasis and the related processes of cell adhesion, invasion, and migration through effects upon the actin cytoskeleton.;In this dissertation, we provide precedent for HSP27 increasing PCa metastasis as well as primary tumor mass. In vitro studies examined the mechanism of HSP27-induced metastatic behavior. The results showed that HSP27 did not affect cell detachment, cell adhesion, or cell migration, but did increase cell invasion. HSP27-driven cell invasion was then determined to be dependent upon matrix metalloproteinase 2 (MMP-2), whose gene expression was increased by HSP27. In vivo, HSP27 altered MMP-2 gene expression in tumors as well. We also examined the effect of HSP27 on the epithelial-to-mesenchymal transition (EMT) of human PCa cells, and found variable changes in vimentin and E-cadherin expression in PC3-M and DU145 cell lines and in PCa tumors.;These findings are consistent with the hypothesis that HSP27 drives the metastatic spread of cancer cells out of the prostate gland to distant sites, does so across a spectrum of expression levels, and identifies HSP27-driven increases in MMP-2 expression as functionally relevant.