β2-microglobulin signaling blockade inhibited androgen receptor axis and caused apoptosis in human prostate cancer cells

Purpose: beta 2-Microglobulin (beta 2M) has been shown to promote osteomimicry and the proliferation of human prostate cancer cells. The objective of this study is to determine the mechanism by which targeting beta 2M using anti-beta 2M antibody inhibited growth and induced apoptosis in prostate cancer cells. Experimental Design: Polyclonal and monoclonal beta 2M antibodies were used to interrupt beta 2M signaling in human prostate cancer cell lines and the growth of prostate tumors in mice. The effects of the beta 2M antibody on a survival factor, androgen receptor (AR), and its target gene, prostate-specific antigen (PSA) expression, were investigated in cultured cells and in tumor xenografts. Results: The beta 2M antibody inhibited growth and promoted apoptosis in both AR-positive and PSA-positive, and AR-negative and PSA-negative, prostate cancer cells via the down-regulation of the AR in AR-positive prostate cancer cells and directly caused apoptosis in AR-negative prostate cancer cells in vitro and in tumor xenografts. The beta 2M antibody had no effect on AR expression or the growth of normal prostate cells. Conclusions: beta 2M downstream signaling regulates AR and PSA expression directly in AR-positive prostate cancer cells. In both AR-positive and AR-negative prostate cancer cells, interrupting beta 2M signaling with the beta 2M antibody inhibited cancer cell growth and induced its apoptosis. The beta 2M antibody is a novel and promising therapeutic agent for the treatment of human prostate cancers.