Protracted treatment with phorbol ester modulates J-7 human hepatoma-cell-induced aggregation and coagulation of human platelet-rich plasma.
In heparinized human platelet-rich plasma (PRP), J-7 human hepatoma cells initially induced platelet aggregation; then a clot formed. ADP-scavenger systems, apyrase and creatine phosphate/creatine phosphokinase did not inhibit this tumor-cell-induced platelet aggregation (TCIPA), whereas hirudin and concanavalin A completely blocked it. J-7 cells also shortened the recalcification time of normal and of Factor-VIII- and IX-deficient human plasma, although it was inactive in shortening the recalcification time of Factor-VII-deficient plasma. After treatment with phorbol 12,13-dibutyrate (PDBu) for 5 to 90 min, the aggregation and coagulation abilities of J-7 cells were unaffected. Prolonged treatment of J-7 cells with PDBu but not with alpha-PDBu for 24 and 72 hr resulted in gradual loss of aggregation and coagulation. Staurosporine antagonized the effect of PDBu and restored aggregation and coagulation in J-7 cells. Protracted treatment with PDBu (24 or 72 hr) did not affect adherence of J-7 cells to the extracellular-matrix proteins (i.e., fibrinogen, fibronectin, laminin, vitronectin and collagen types I and IV) or to the surface of plastic culture dishes. The treatment also did not affect J-7 cell detachment from plastic culture dishes. These in vitro results demonstrate that protracted phorbol ester treatment diminishes TCIPA and blood coagulation of tumor cells.
Ko
F N
FN
Pharmacological Institute, College of Medicine, National Tawian University, Taipei.
Yu
S M
SM
Teng
C M
CM
D000470:Alkaloids / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000503:physiopathology*; D002448:Cell Adhesion / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005164:Factor IX / Q000502:physiology; D005167:Factor VII / Q000502:physiology; D006493:Heparin / Q000494:pharmacology; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D008113:Liver Neoplasms / Q000503:physiopathology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D019311:Staurosporine; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D016326:Extracellular Matrix Proteins; D006629:Hirudins; D003208:Concanavalin A; D015240:Phorbol 12,13-Dibutyrate; D005167:Factor VII; D005164:Factor IX; D006493:Heparin; D019311:Staurosporine