Inhibitors of collagenase IV and cell adhesion reduce the invasive activity of malignant tumour cells.
The invasive activities of some malignant cells appear to be activated by contact with laminin. This protein occurs solely in basement membranes and the binding of malignant cells to the surface of this extracellular matrix initiates the invasion process. Passage of the cells across basement membrane requires degradative activity and laminin induces the production of collagenase IV which lyses the collagen IV network. The motility of the cells is enhanced by chemo-attractants and by matrix molecules. Peptides that inhibit the binding of tumour cells to laminin, inhibitors of collagenase IV, and inhibitors of specific pathways of arachidonic acid metabolism prevent invasion as well as the metastasis of malignant cells and could be employed to stop the spread of cancer.
Reich
R
R
Laboratory of Developmental Biology and Anomalies, National Institute of Dental Research, Bethesda, Maryland 20892.
Stratford
B
B
Klein
K
K
Martin
G R
GR
Mueller
R A
RA
Fuller
G C
GC
D000818:Animals; D001485:Basement Membrane / Q000032:analysis; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen / Q000032:analysis; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007797:Laminin / Q000032:analysis / Q000494:pharmacology; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009362:Neoplasm Metastasis / Q000473:pathology*; D011509:Proteoglycans / Q000032:analysis; D019714:Tissue Inhibitor of Metalloproteinases
D004791:Enzyme Inhibitors; D007797:Laminin; D011509:Proteoglycans; D019714:Tissue Inhibitor of Metalloproteinases; D003094:Collagen; D003012:Microbial Collagenase