PLASMINOGEN DEPENDENT LAMININ DEGRADATION AND MATRIGEL INVASION BY CULTURED COLON CANCER IS DIRECTED BY RECEPTOR-BOUND UROKINASE

Breach of the basement is thought to represent one of the first steps in tumour metastasis. The major basement membrane components are laminin, a glycoprotein, and type IV collagen. Plasmin not only degrades laminin, but also activates the collagen-degrading enzyme collagenase. Thus, plasminogen activators such as urokinase might be expected to play a major role in basement membrane breakdown and, hence, in tumour metastasis. This paper presents evidence that the crucial factor in tumour cells' ability to penetrate the basement membrane is urokinase bound to the cell surface via urokinase receptors. For the large majority of cultured colonic cell lines tested, the ability to penetrate a film of basement membrane material (Matrigel(R)) correlated directly with the number of cell surface receptors charged with urokinase. One line which expressed higher receptor levels could be made to invade the extra cellular matrix by charging these binding sites with exogeneous urokinase. The most convincing evidence, however, is that the tumour cells' ability to penetrate the Matrigel(R)) could be significantly impaired either by antibodies to the urokinase A chain or by a synthetic peptide which blocks the interaction of urokinase with its receptors.