Evidence for increased activated metalloproteinase 2 (MMP-2a) expression associated with human prostate cancer progression.
Immunolabeling studies have previously indicated that increased expression of the 72-kDa matrix metalloproteinase 2 (MMP-2) is associated with human prostate cancer progression. It is not known if the enzymatically active MMP-2 is expressed in prostate cancer and if increased expression is associated with progression. Monoclonal antibodies specific for the activated MMP-2 molecule (MMP-2a, 66 kDa) were used (along with previously developed MMP-2 antibodies) to investigate the expression of MMP-2a and MMP-2 in human prostate tissue extracts. SDS-PAGE, Western blots, and zymography indicated that MMP-2a expression was undetectable 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 lymph node metastases (n = 7). Quantitative ELISAs of human prostate cancer tissue extracts revealed that the levels of MMP-2 and MMP-2a per microgram of protein increased in prostate cancer tissues of increased GS (n = 48). MMP-2a levels were also high in prostatic lymph node metastases, but MMP-2 was not expressed or was barely detectable in these tissues. 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 increases in MMP-2a are associated with the malignant progression of prostate cancer and with tumor cell metastases to lymph nodes.
Stearns
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Department of Pathology, Medical College of Pennsylvania, Philadelphia 19129, USA.
Stearns
M E
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D015153:Blotting, Western; D018450:Disease Progression; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D011467:Prostate / Q000201:enzymology*; D011470:Prostatic Hyperplasia / Q000201:enzymology*; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology
D009363:Neoplasm Proteins; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2