Abstract
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 form metastatic tumors at distant sites. Heat shock protein 27 (HSP27) is known to increase human PCa cell invasion and its overexpression is associated with metastatic disease. The role of HSP27 in driving PCa cell movement from the prostate to distant metastatic sites is unknown. Increased HSP27 expression increased metastasis as well as primary tumor mass. In vitro studies further examined the mechanism of HSP27-induced metastatic behavior. HSP27 did not affect cell detachment, adhesion, or migration, but did increase cell invasion. Cell invasion was dependent upon matrix metalloproteinase 2 (MMP-2), whose expression was increased by HSP27. In vivo, HSP27 induced commensurate changes in MMP-2 expression in tumors. These findings demonstrate that HSP27 drives metastatic spread of cancer cells from the prostate to distant sites, does so across a continuum of expression levels, and identifies HSP27-driven increases in MMP-2 expression as functionally relevant. These findings add to prior studies demonstrating that HSP27 increases PCa cell motility, growth and survival. Together, they demonstrate that HSP27 plays an important role in PCa progression.
Highlights
Prostate cancer (PCa) is the second most common cause of cancer-related death and the most commonly diagnosed form of cancer for American males [1]
Over expressing cell lines were sub-classified as moderate-level overexpression (HSP27-WT-M), if their level of Heat shock protein 27 (HSP27) expression was between 200% and 300% of that of the average of vector control cells, and as high-level overexpression (HSP27WT-H), if levels were above 300%
We demonstrate for the first time that HSP27 increases the movement of human PCa cells out of the prostate gland resulting in the formation of distant metastasis
Summary
Prostate cancer (PCa) is the second most common cause of cancer-related death and the most commonly diagnosed form of cancer for American males [1]. PCa mortality is caused by the movement of cancer cells from their point of origin within the prostate gland to multiple distant organ sites throughout the body [1]. Heat shock protein 27 (HSP27) expression has been associated with PCa progression, and in the development of metastasis in particular, in several clinical studies [3,4,5,6]. PCa progression, with highest expression found in metastatic PCa [7,8,9,10]. HSP27 was found to be an independent predictor of poor clinical outcome for PCa [6, 10]
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