Changes in beta-2 microglobulin expression in prostate cancer

Abstract

Increased shedding of beta-2 microglobulin (B2m, 11.8 kDa), a component of the major histocompatibility complex class I (MHC I), by tumor cells has significance with regard to escape from immune-surveillance, cellular proliferation, and tumor development and progression. Aberrant expression of MHC I is known to occur in prostate cancer (PCa) but not in benign prostatic hyperplasia. We have determined B2m released by PCa cells in culture and in the urine of 101 patients with advanced PCa by Western blotting and radioimmunoassay. B2m levels in the conditioned medium of human PCa cell lines and primary cultures derived from distant metastasis as well as in the urine of patients with bone and visceral metastasis were higher than normal and also higher than those from patients with local/regional extensions of the disease. In the group of patients with bone metastasis (66 patients), high urine B2m was associated with significantly shortened survival. In addition to the 11.8 kDa B2m, a high molecular weight B2m immunoreactivity of approximately 38 kDa was found in highly tumorigenic PC-3 cell line, but not in the relatively indolent DU-145 and LNCaP human PCa cell lines. The approximately 38 kDa B2m was found in the urine of several PCa patients but not of healthy controls examined by Western analysis. The conditioned medium of a prostatic small cell carcinoma cell line, NCI-H660, had high levels of chromogranin A and B2m, but prostate specific antigen was absent. In conclusion, increased B2m shedding was associated with distant metastasis of PCa and an abnormal B2m immunoreactivity was found in PCa.