Journal
BRITISH JOURNAL OF CANCER
Volume 106, Issue 10, Pages 1689-1696Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2012.138
Keywords
prostate cancer; metastasis; statins; bone marrow stroma
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BACKGROUND: Although statins do not affect the incidence of prostate cancer (CaP), usage reduces the risk of clinical progression and mortality. Although statins are known to downregulate the mevalonate pathway, the mechanism by which statins reduce CaP progression is unknown. METHODS: Bone marrow stroma (BMS) was isolated with ethical approval from consenting patients undergoing surgery for nonmalignant disease. PC-3 binding, invasion and colony formation within BMS was assessed by standardised in vitro co-culture assays in the presence of different statins. RESULTS: Statins act directly on PC-3 cells with atorvastatin, mevastatin, simvastatin (1 mu M) and rosuvastatin (5 mu M), but not pravastatin, significantly reducing invasion towards BMS by an average of 66.68% (range 53.93-77.04%; P<0.05) and significantly reducing both number (76.2 +/- 8.29 vs 122.9 +/- 2.48; P = 0.0055) and size (0.2 +/- 0.0058mm(2) vs 0.27 +/- 0.012mm(2); P = 0.0019) of colonies formed within BMS. Statin-treated colonies displayed a more compact morphology containing cells of a more epithelial phenotype, indicative of a reduction in the migrational ability of PC-3 cells. Normal PC-3 phenotype and invasive ability was recovered by the addition of geranylgeranyl pyrophosphate (GGPP). CONCLUSION: Lipophilic statins reduce the migration and colony formation of PC-3 cells in human BMS by inhibiting GGPP production, reducing the formation and the spread of metastatic prostate colonies. British Journal of Cancer (2012) 106, 1689-1696. doi:10.1038/bjc.2012.138 www.bjcancer.com Published online 24 April 2012 (C) 2012 Cancer Research UK
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