PURPOSE: beta2-Microglobulin (beta2M) 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 beta2M using anti-beta2M antibody inhibited growth and induced apoptosis in prostate cancer cells. EXPERIMENTAL DESIGN: Polyclonal and monoclonal beta2M antibodies were used to interrupt beta2M signaling in human prostate cancer cell lines and the growth of prostate tumors in mice. The effects of the beta2M 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 beta2M 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 beta2M antibody had no effect on AR expression or the growth of normal prostate cells. CONCLUSIONS: beta2M 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 beta2M signaling with the beta2M antibody inhibited cancer cell growth and induced its apoptosis. The beta2M antibody is a novel and promising therapeutic agent for the treatment of human prostate cancers.
PURPOSE:beta2-Microglobulin (beta2M) has been shown to promote osteomimicry and the proliferation of humanprostate cancer cells. The objective of this study is to determine the mechanism by which targeting beta2M using anti-beta2M antibody inhibited growth and induced apoptosis in prostate cancer cells. EXPERIMENTAL DESIGN: Polyclonal and monoclonal beta2M antibodies were used to interrupt beta2M signaling in humanprostate cancer cell lines and the growth of prostate tumors in mice. The effects of the beta2M 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 beta2M 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 beta2M antibody had no effect on AR expression or the growth of normal prostate cells. CONCLUSIONS:beta2M 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 beta2M signaling with the beta2M antibody inhibited cancer cell growth and induced its apoptosis. The beta2M antibody is a novel and promising therapeutic agent for the treatment of humanprostate cancers.
Authors: Peter S Nelson; Nigel Clegg; Hugh Arnold; Camari Ferguson; Michael Bonham; James White; Leroy Hood; Biaoyang Lin Journal: Proc Natl Acad Sci U S A Date: 2002-08-16 Impact factor: 11.205
Authors: M Vitale; R Rezzani; L Rodella; G Zauli; P Grigolato; M Cadei; D J Hicklin; S Ferrone Journal: Cancer Res Date: 1998-02-15 Impact factor: 12.701
Authors: Takeo Nomura; Wen-Chin Huang; Haiyen E Zhau; Daqing Wu; Zhihui Xie; Hiromitsu Mimata; Majd Zayzafoon; Andrew N Young; Fray F Marshall; M Neale Weitzmann; Leland W K Chung Journal: Clin Cancer Res Date: 2006-12-15 Impact factor: 12.531
Authors: J A Ruizeveld de Winter; P J Janssen; H M Sleddens; M C Verleun-Mooijman; J Trapman; A O Brinkmann; A B Santerse; F H Schröder; T H van der Kwast Journal: Am J Pathol Date: 1994-04 Impact factor: 4.307
Authors: Sajni Josson; Takeo Nomura; Jen-Tai Lin; Wen-Chin Huang; Daqing Wu; Haiyen E Zhau; Majd Zayzafoon; M Neale Weizmann; Murali Gururajan; Leland W K Chung Journal: Cancer Res Date: 2011-03-22 Impact factor: 12.701