Plasminogen activator production by human tumor cells: effect on tumor cell-extracellular matrix interactions.
Cell lines derived from 3 different types of human tumor (e.g., squamous carcinomas, melanomas and gliomas) were examined for production of plasminogen activator activity and for attachment and spreading on various extracellular matrix components in the presence or absence of plasminogen. All of the squamous carcinoma and melanoma lines produced high levels of plasminogen activator activity. In contrast, 4 of 6 glioma lines had undetectable activity. Cells from all 3 tumor types attached and spread on fibrinogen-coated or fibrin-coated plastic dishes in the absence of plasminogen. In the presence of exogenous plasminogen, the attachment and spreading of the cells which produced high levels of plasminogen activator activity was inhibited. The plasminogen activator-deficient cells were much less sensitive to exogenous plasminogen. In the presence of plasminogen, attachment and spreading on fibronectin-coated dishes was also partially inhibited. In contrast, plasminogen had no effect on the attachment and spreading of the cells on type-I or -IV collagen, laminin or thrombospondin. Previous studies have shown that tumor-cell adhesion to the extracellular matrix depends on the synthesis of receptors for extracellular matrix components or on the synthesis of extracellular matrix components themselves. The present study shows that, in addition, the production of enzymes which are capable of degrading these components also influences tumor-cell adhesion to extracellular matrix moieties.
Varani
J
J
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109.
McKeever
P E
PE
Fligiel
S E
SE
Sitrin
R G
RG
D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects*; D003094:Collagen; D005109:Extracellular Matrix / Q000187:drug effects*; D005353:Fibronectins; D005910:Glioma / Q000378:metabolism / Q000473:pathology; D006023:Glycoproteins; D006801:Humans; D007797:Laminin; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010958:Plasminogen / Q000494:pharmacology; D010960:Plasminogen Activators / Q000096:biosynthesis*; D019699:Thrombospondins; D014407:Tumor Cells, Cultured / Q000378:metabolism* / Q000473:pathology
D005353:Fibronectins; D006023:Glycoproteins; D007797:Laminin; D009363:Neoplasm Proteins; D019699:Thrombospondins; D010958:Plasminogen; D003094:Collagen; D010960:Plasminogen Activators