Plasminogen activator and matrix metalloproteinase production and extracellular matrix degradation by rat prostate cancer cells in vitro: correlation with metastatic behavior in vivo.

ABSTRACT

BACKGROUND: The plasminogen activation (PA) and metalloproteinase (MMP) system are involved in tumor cell migration and invasion. METHODS: The proteolytic activity of cell lines originating from the rat Dunning R-3327 prostate tumor was analyzed by measuring in vitro extracellular matrix degradation, enzyme activity, and mRNA levels of enzymes, inhibitors, and receptors, and compared with their known metastatic behavior in vivo. RESULTS: Only the highly metastatic sublines AT-3, MATLu, and MATLyLu showed a high extracellular matrix degradation mediated by urokinase-type plasminogen activator (u-PA). Relatively high levels of u-PA were present in the aggressive cell lines. u-PA receptor mRNA was produced in all cells, and all but AT-1 produced LDL-receptor-related-protein (LRP) mRNA. t-PA mRNA was only found in HIF and MATLu. In gelatin, zymography lysis was observed at 72 kD and 74-76 kD in MATLu and MATLyLu cells, respectively. MMP-2 mRNA was present in all cell lines except AT-1 and AT-2, and MMP-3 mRNA was present in AT-2, AT-3, and MATLu. CONCLUSIONS: These in vitro experiments show that in different rat prostate cancer sublines, proteolytic activity and u-PA-mediated extracellular matrix degradation correlate with their known metastatic behavior in vivo.