Cell signalling associated with fibrinolytic ligand binding to human colorectal carcinoma cells.
Addition of purified plasmin or plasminogen (0.1 microM) to serum-free culture media elevated cellular D-myo-inositol 1,4,5-trisphosphate (InsP3) levels in human colorectal carcinoma cells within 1 h to double those of control cells. This was accompanied by decreases in cellular phosphatidylinositol bisphosphate by 40% in cells exposed to fibrinolytic ligands for up to 1 h. The effect was not due to opening of Ca2+ channels of the type blocked by 5 microM nifedipine, and 100 microM EGTA, a Ca2+ chelator, did not suppress plasmin's ability to elevate InsP3. Binding assays at 4 degrees C with 125I-labelled plasmin indicated maximum binding within 1 h suggesting that the effects of plasmin may be associated with its cell-binding function. These cells could convert exogenous plasminogen to plasmin with endogenous activation and this was accompanied by a decrease in radioactive phosphatidylinositol well below control levels (13% of control). Our results contribute to evidence for the association of plasmin-binding sites with a signalling system. A cell signalling system indirectly or directly associated with plasmin binding, would permit carcinoma cells to coordinate extracellular fibrinolysis with cell migration and motility through second messengers.
Liepkalns
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V
Institut de Recherche Scientifique sur le Cancer-CNRS, B.P., Villejuif, France.
Durand
H
H
Bougeret
C
C
D002450:Cell Communication / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D004533:Egtazic Acid / Q000494:pharmacology; D005341:Fibrinolysin / Q000378:metabolism*; D005342:Fibrinolysis / Q000502:physiology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007295:Inositol Phosphates / Q000096:biosynthesis; D009361:Neoplasm Invasiveness / Q000473:pathology; D009543:Nifedipine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D004533:Egtazic Acid; D015544:Inositol 1,4,5-Trisphosphate; D010958:Plasminogen; D005341:Fibrinolysin; D009543:Nifedipine