Laminin degradation by human colon carcinoma cells: a role for urinary and tissue plasminogen activators

The human colon carcinoma cell lines Co112 and Co115 are both invasive in nude mice following intraperitoneal implantation. Co115 cells only exhibit metastasis capacity under this condition. Characterization of the plasminogen activation system demonstrates that Co112 cells express the urinary-type plasminogen activator (uPA) and Co115 cells the tissue-type (tPA), exclusively. Immunocytochemical analyses revealed that the in vitro plasminogen-dependent lysis of exogenous basement membrane laminin induced by Co112 cells displayed a gradient-like pattern, whereas, in the case of Co115 cells, it was sharply confined to the pericellular area. Double-labeling experiments showed that uPA on Co112 and tPA on Co115 cells are cell-surface-associated constituents. The cellular distribution of laminin expressed by tumor cells themselves appears to be distributed homogeneously in the cytoplasm of both cell types. We suggest that the extracellular matrix degradation induced by tumor cell surface-associated plasmin implies two different mechanisms which are specifically related to uPA or to tPA, both contributing to matrix degradation and malignant invasion.