EFFECTS OF INHIBITORS OF PLASMINOGEN-ACTIVATOR, SERINE PROTEINASES, AND COLLAGENASE-IV ON THE INVASION OF BASEMENT-MEMBRANES BY METASTATIC CELLS

  • 15 June 1988
    • journal article
    • research article
    • Vol. 48  (12) , 3307-3312
Abstract
Using both human and murine cell lines, we show that malignant cells are able to invade through basement membrane and also secrete elevated amounts of collagenase IV, an enzyme implicated in the degration of basement membranes. Using serine proteinase inhibitors and antibodies to plasminogen activators as well as a newly described collagenase inhibitor we demonstrate that a protease cascade leads to the activation of an enzyme(s) that cleaves collagen IV. Inhibition at each step reduces the invasion of the tumor cells through reconstituted basement membrane in vitro. Treatment with a collagenase inhibitor reduced the incidence of lung lesions in mice given i.v. injections of malignant melanoma cells.