TitleInduction of proinflammatory response in prostate cancer epithelial cells by activated macrophages.
Publication TypeJournal Article
Year of Publication2009
AuthorsWong, CP, Bray, TM, Ho, E
JournalCancer letters
Date Published2009 Apr 8
KeywordsVascular Cell Adhesion Molecule-1

Emerging evidence indicates that chronic inflammation plays an important role in prostate carcinogenesis. Yet to date the precise molecular and cellular mechanisms linking inflammation to carcinogenesis remains unclear. The purpose of this study was to determine the local contribution of prostate epithelial cells to the inflammatory process. We characterized the inflammatory response elicited directly by prostate epithelial cells using an in vitro culture system in which androgen-dependent LNCaP prostate cancer epithelial cells were exposed to conditioned media from LPS-activated THP-1 macrophages. Upon exposure to activated macrophage conditioned media, LNCaP cells elicited a local proinflammatory response, as evidenced by NFkappaB activation, and the production of proinflammatory cytokines TNFalpha, IL-1beta, and IL-6. Furthermore, we observed a significant upregulation of the adhesion molecule VCAM-1 and nuclear estrogen receptor alpha (ERalpha) two biomarkers that correlate with tumor immune evasion and tumor progression. Our results suggest that prostate epithelial cells may play a significant role in sustaining and amplifying the inflammation process through NFkappaB activation and local production of proinflammatory cytokines that results in the recruitment and activation of additional immune cells in the prostate. At the same time, increased expression of VCAM-1 and ERalpha in prostate epithelial cells upon exposure to inflammatory conditions highlights the potential link between chronic inflammation and its involvement in promoting prostate cancer carcinogenesis.