title: TNF-alpha protects dendritic cells from prostate cancer-induced apoptosis.
abstract: We have recently shown that human prostate cancer (PCa) cells induced apoptotic death of the most potent antigen-presenting cells, dendritic cells (DC), which are responsible for the induction of specific antitumor immune responses. Here we have evaluated the effect of murine PCa cells RM-1 on the survival of immature and tumor necrosis factor-alpha (TNF-alpha)-stimulated mature DC. PCa cells and DC were co-incubated for 24-48 h and DC apoptosis was assessed by morphologic criteria, Annexin V assay, and TUNEL staining. We have shown that co-incubation of RM-1 cells with DC is accompanied by an increased level of DC apoptosis, which was mediated by decreased expression of anti-apoptotic protein Bcl-2. Stimulation of DC maturation by TNF-alpha resulted in increased resistance of DC to PCa-induced apoptosis. In TNF-alpha treated mature DC, but not in immature DC, the expression of Bcl-2 was not blocked after exposure to RM-1-derived factors. Thus, these data suggest that TNF-alpha-induced maturation of DC increases their resistance to PCa induced apoptosis. This is likely to be due to the stabilizing of the expression of anti-apoptotic protein Bcl-2. The difference in the sensitivity of mature and immature DC to PCa-induced cell death should be considered during the design of DC-based clinical trials for PCa patients.Prostate Cancer and Prostatic Diseases (2001) 4, 221-227.
authors.affiliation: Department of Urology, University of Pittsburgh Medical Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Pirtskhalaishvili
authors.forename: G V
authors.initials: GV
authors.lastname: Shurin
authors.forename: C
authors.initials: C
authors.lastname: Esche
authors.forename: D L
authors.initials: DL
authors.lastname: Trump
authors.forename: M R
authors.initials: MR
authors.lastname: Shurin