Roles of renin-angiotensin system in the regulation of prostate cancer bone metastasis: a critical review

Abstract

Mestastatic prostate cancer cells (MPCCs) frequently metastasize to bone, which is a “favorite soil” for colonization and proliferation of MPCCs. Prostate cancer bone mestastasis is tightly associated with tumor-induced bone lesions, most commonly caused from (1) the etiological imbalance between osteoblastic bone formation and osteoclastic bone resorption and from (2) the anti-tumor immune response. Therefore, understanding of prostate cancer biology and prostate cancer bone metastasis has led to the establishment of drug development programs for treatment of the patients with bone metastasis. The renin-angiotensin system (RAS) controls systemic body fluid circulation; nonetheless, the existence of a local RAS in tumors has been reported. Importantly, the local RAS has recently emerged as a potential regulator of tumorigenesis and cancer metastasis. This review summarizes and dissects the critical roles of the local RAS in promoting (1) progression of metastatic prostate cancer, and (2) development and progression of PCa bone metastasis, thereby providing multiple solutions for the potential therapeutic intervention.