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Plasminogen-Activator Inhibitor Type 1 is a Potent Natural Inhibitor of Extracellular Matrix Degradation by Fibrosarcoma and Colon Carcinoma Cells

Cajot, J. F. ; Bamat, J. ; Bergonzelli, G. E. ; Kruithof, E. K. O. ; Medcalf, R. L.

Proceedings of the National Academy of Sciences - PNAS, 1990-09, Vol.87 (18), p.6939-6943 [Periódico revisado por pares]

Washington, DC: National Academy of Sciences of the United States of America

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Título:
Plasminogen-Activator Inhibitor Type 1 is a Potent Natural Inhibitor of Extracellular Matrix Degradation by Fibrosarcoma and Colon Carcinoma Cells
Autor: Cajot, J. F. ; Bamat, J. ; Bergonzelli, G. E. ; Kruithof, E. K. O. ; Medcalf, R. L.
Assuntos: Animals ; Antibodies ; Biological and medical sciences ; Carcinoma ; Carcinoma, Hepatocellular ; Cell Line ; Cell lines ; Cell membranes ; Cell physiology ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Cells ; Coculture techniques ; Colonic Neoplasms - metabolism ; Complementary DNA ; Endothelial cells ; extracellular matrix ; Extracellular Matrix - metabolism ; Extracellular Matrix - ultrastructure ; Fibrosarcoma - metabolism ; Fundamental and applied biological sciences. Psychology ; Humans ; Kinetics ; L cells ; L Cells (Cell Line) - metabolism ; Liver Neoplasms ; Mice ; Molecular and cellular biology ; Plasminogen Activators - isolation & purification ; Plasminogen Activators - metabolism ; Plasminogen Inactivators - isolation & purification ; Plasminogen Inactivators - metabolism ; Transfection ; Tumors
É parte de: Proceedings of the National Academy of Sciences - PNAS, 1990-09, Vol.87 (18), p.6939-6943
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Descrição: We have analyzed the role of plasminogen-activator inhibitor type 1 (PAI-1) in the regulation of tumor cell-mediated extracellular matrix degradation. Immunocytochemical analysis revealed PAI-1 associated with microgranular and fibrillar material of the extracellular matrix and demonstrated the presence of PAI-1 as a cell surface-associated antigen. Transforming growth factor β significantly reduced matrix degradation mediated by HT-1080 human fibrosarcoma cells. This inhibition was correlated with an increase in PAI-1 antigen expression, whereas urinary-type plasminogen activator (u-PA) secretion was unaffected. In this experimental system, PAI-1 regulated extracellular matrix breakdown, as added PAI-1 inhibited matrix solubilization, whereas monoclonal antibodies to PAI-1 increased it. A cell line (LPAI) producing high levels of biologically active PAI-1 was established by transfection of a human PAI-1 cDNA clone into mouse L cells. Coculture experiments demonstrated that LPAIcells prevented matrix degradation by Lu-PAcells (L cells expressing high levels of u-PA) or Co-115 human colon carcinoma cells (expressing tissue-type plasminogen activator). These results indicate that PAI-1 may play a critical role in the regulation of extracellular matrix degradation during tumor cell invasion.
Editor: Washington, DC: National Academy of Sciences of the United States of America
Idioma: Inglês

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Plasminogen-Activator Inhibitor Type 1 is a Potent Natural Inhibitor of Extracellular Matrix Degradation by Fibrosarcoma and Colon Carcinoma Cells

Cajot, J. F. ; Bamat, J. ; Bergonzelli, G. E. ; Kruithof, E. K. O. ; Medcalf, R. L.

Washington, DC: National Academy of Sciences of the United States of America

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