Roles of IL-6/STAT3 and IL-1 Beta Signaling in Prostate Cancer

Inhibiting androgen receptor (AR) signaling by hormone deprivation therapy through surgical or medical castration is initially effective for prostate cancer, but ultimately leads to a hormone-resistant (HR) phenotype. In the clinic, HR cancers are usually highly aggressive and respond poorly to treatment. We previously reported that HR prostate cancer cells appeared more aggressive behaviors and more radioresistance compared to hormone- sensitive prostate cancer. A better understanding of the molecular mechanisms involved in HR could provide insight into tumor progression and lead to more rational approaches to therapy. Several mechanisms are implicated in prostate cancer progression and androgen-independent growth, involving AR gene mutation, overexpression or ligand- independent activation, AKT/mTOR and IL-6/STAT3 signaling. We previously reported that constitutional activation of STAT3 combined with increased MDM2 and decreased p53 is associated with the transition of HR prostate cancer. IL-6, a multifunctional cytokine, is a major activator of signaling pathway of JAK/ STAT3. IL-6 signaling is implicated in the regulation of tumor growth and metastatic spread, and its level could be correlated with a poor prognosis in different cancers. Epidemiologic and experimental evidence supports the concept that chronic inflammation promotes the development and progression of cancers. An increase in inflammatory mediators has been shown to lead to tumor promotion, invasion, and angiogenesis. The main cytokines influencing the acute phase protein response in humans include IL-6 and IL-1β. IL-6 is the main inducer, and IL-1βcan induce IL-6 production from tumor cells and host cells. IL-1β and IL-6 has been demonstrated to be elevated in a variety of tumors, and contribute to tumor proliferation, metastasis and tumor resistance. Furthermore, the induction, expansion, and retention of MDSC are due to several different factors, including potent inflammatory mediators. IL-6 is an important proinflammatory cytokine and a main inducer of inflammation. In the present study, we aimed to investigate the role of IL-6/stat3 signaling, MDSC and IL-1 beta in the prognosis of prostate cancer by immunochemical staining analysis in addition to cellular and animal experiments.

Project ID:PC10301-1142
External Project ID:NSC101-2314-B182-062-MY3