EVIDENCE FOR INCREASED ACTIVATED METALLOPROTEINASE-2 (MMP-2A) EXPRESSION ASSOCIATED WITH HUMAN PROSTATE-CANCER PROGRESSION

Immunolabeling studies have previously indicated that increased expres sion of the 72-kDa matrix metalloproteinase 2 (MMP-2) is associated wi th human prostate cancer progression. It is not known if the enzymatic ally active MMP-2 is expressed in prostate cancer and if increased exp ression is associated with progression. Monoclonal antibodies specific for the activated MMP-2 molecule (MMP-2a, 66 kDa) were used (along wi th previously developed MMP-2 antibodies) to investigate the expressio n of MMP-2a and MMP-2 in human prostate tissue extracts. SDS-PAGE, Wes tern blots, and zymography indicated that MMP-2a expression was undete ctable in normal prostate (n = 6), benign prostatic hyperplasia (n = 9 ), and in prostate cancer of low Gleason score (GS) 4 (n = 11). MMP-2a was expressed in prostate cancer of increased GS (n = 37) and in lymp h node metastases (n = 7). Quantitative ELISAs of human prostate cance r tissue extracts revealed that the levels of MMP-2 and MMP-2a per mic rogram of protein increased in prostate cancer tissues of increased GS (n = 48). MMP-2a levels were also high in prostatic lymph node metast ases, bur MMP-2 was not expressed or was barely detectable in these ti ssues. The molar ratios of MMP-2a to MMP-2 increased from 0 to 6.23 in tissues of GS 4 to 10, respectively. We conclude that significant inc reases in MMP-2a are associated with the malignant progression of pros tate cancer and with tumor cell metastases to lymph nodes.