Stamp2 Expression Mediated By Cytokines Attenuates Their Growth-Limiting Effects In Prostate Cancer Cells

Simple SummaryProstate cancer (PCa) is the most common non-skin cancer and one of the leading causes of cancer death in men. Despite significant developments in therapy options with improved survival, no curative treatment is currently available. We have previously identified six transmembrane protein of prostate 2 (STAMP2) as an important factor for PCa growth and survival. We now show that STAMP2 expression is regulated by inflammatory signaling, which has recently been implicated in PCa. Two proinflammatory cytokines, interleukin 6 and interleukin 1 beta, synergize with each other to induce STAMP2 expression. Interestingly, STAMP2 knockdown increased the sensitivity of PCa cells to cytokine treatment. Thus, STAMP2 that acts as a survival factor in PCa, is both independently and synergistically regulated by inflammatory signaling that may affect disease progression.Inflammatory events and dysregulated cytokine expression are implicated in prostate cancer (PCa), but the underlying molecular mechanisms are poorly understood at present. We have previously identified six transmembrane protein of the prostate 2 (STAMP2, also known as STEAP4) as an androgen-regulated gene, as well as a key regulator of PCa growth and survival. STAMP2 is also regulated by, and participates in, inflammatory signaling in other tissues and pathologies. Here, we show that the proinflammatory cytokines interleukin 6 (IL-6) and Interleukin 1 beta (IL-1 beta) significantly increase and strongly synergize in promoting STAMP2 expression in PCa cells. The two cytokines increase androgen-induced STAMP2 expression, but not expression of other known androgen target genes, suggesting a unique interplay of androgens and cytokines in regulating STAMP2 expression. Interestingly, STAMP2 knockdown significantly increased the ability of IL-6 and IL-1 beta to inhibit PCa cell growth in vitro. These results suggest that STAMP2 may represent a unique node through which inflammatory events mediate their effects on PCa growth and survival.