Modulation of the malignant phenotype with the urokinase-type plasminogen activator and the type I plasminogen activator inhibitor.
Gene transfer techniques were utilized to evaluate the role of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) in enhancing or preventing the expression of the invasive malignant phenotype, respectively. Mouse L-cell transfectants expressing human uPA or human PAI-1 as well as mouse B16 transfectants expressing mouse uPA or human PAI-1 were generated. These transfectants were tested using a variety of experimental methods including smooth muscle cell matrix solubilization in vitro, lung colony formation in vivo and co-cultures of antagonist-expressing cells in vitro. Results from these studies provide direct evidence for an enhancing role of uPA in malignant invasion and experimental metastasis and for a modulatory role of PAI-1 in tumor cell-mediated breakdown of extracellular matrices.
Sordat
B
B
Unit of Experimental Pathology, Swiss Institute for Experimental Cancer Research, Epalinges.
Reiter
L
L
Cajot
J F
JF
D000818:Animals; D003110:Colonic Neoplasms / Q000473:pathology; D005109:Extracellular Matrix / Q000187:drug effects*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics; D006358:Hot Temperature; D006801:Humans; D007739:L Cells / Q000187:drug effects* / Q000473:pathology; D008175:Lung Neoplasms / Q000556:secondary; D008546:Melanoma, Experimental / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010641:Phenotype; D010960:Plasminogen Activators / Q000235:genetics / Q000494:pharmacology*; D015849:Plasminogen Inactivators / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000473:pathology / Q000637:transplantation; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000494:pharmacology*
D016326:Extracellular Matrix Proteins; D006360:Heat-Shock Proteins; D015849:Plasminogen Inactivators; D011993:Recombinant Fusion Proteins; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator