Type-1 plasminogen activator inhibitor in human breast carcinomas

We have investigated the occurrence of type-1 inhibitor of plasminogen activators (PAI-1) in human breast tumors. PAI-1 levels, measured by enzyme-linked immunosorbent assay, were significantly higher in malignant breast carcinomas (n = 178) than in benign breast tumors (n = 25). The levels of PAI-1 were found to be correlated with those of urokinase-type plasminogen activator (u-PA). The presence of PAI-1 in tumor extracts was also demonstrated by immunoblotting analysis. Immunohistochemical investigations by the use of monoclonal and polyclonal antibodies showed that PAI-1 was mostly localized in the tumor islands, associated with the tumor cells; in addition, it was present in vessel walls and in normal duct epithelia, but absent from the stroma. Analysis of RNA extracted from tumors by polymerase chain reaction revealed the presence of PAI-1 mRNA. We conclude that PAI-1 is present in human breast carcinoma cells, and that it is--at least partially-- produced locally, either by the cancer cells or by other cells in the tumors. We have previously demonstrated that a high level of u-PA in human breast carcinomas is associated with poor prognosis. These results, combined with our present findings, present 2 possibilities: either the cancer cells need PAI-1 in order to utilize the u-PA-mediated pathway of plasminogen activation for invasion and metastasis; or PAI-1 represents a defense mechanism against tumor invasion.