Involvement of plasminogen activator production with tumor metastasis in a rat model.

The process of metastasis involves numerous steps, many of which are thought to require the action of hydrolases, such as collagenase and other proteases. In this study, we investigate the role of the protease plasminogen activator in the metastasis of the rat mammary adenocarcinoma 13762. We observed that this tumor cell line is heterogeneous with respect to plasminogen activator (PAA) production. Clonal tumor cell populations were isolated which produced various levels of PAA. This phenotypic property of these clones remained stable for long periods of in vitro culture and did not affect their tumorigenicity. When the metastatic potential of these clones was determined using the lung colony assay, a strong correlation between PAA and metastatic potential was found. Furthermore, a threshold level of PAA production was observed, above which the lung colony-forming ability of the cells increased dramatically. These studies suggest that PAA production may play an important role in tumor metastasis.