Role of tissue factor in the antitumor effect of recombinant human tumor necrosis factor-alpha in mice.
Recombinant tumor necrosis factor-alpha (rTNF-alpha) inhibited tumor growth of Meth A fibrosarcoma (Meth A) solid tumor in mice, and the antitumor effect of rTNF-alpha was significantly decreased by pretreatment with small doses or rTNF-alpha in mice. In in vitro experiments, incubation of human umbilical vein endothelial cells with rTNF-alpha enhanced procoagulant activity (PCA), which was drastically augmented after an addition of the conditioned medium of Meth A tumor cells. Furthermore, rTNF-alpha-induced PCA was decreased by pretreatment with rTNF-alpha in endothelial cells. This PCA was completely blocked after the addition of anti-human tissue factor (TF) murine monoclonal antibody. These results imply that in vivo antitumor effects of rTNF-alpha are mediated by expression of TF in endothelial cells, which is augmented by tumor released factor(s).
Nishigaki
F
F
Department of Pharmacology, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Miyayasu
K
K
Tsujimoto
S
S
Manda
T
T
Shimomura
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy*; D006801:Humans; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013154:Spleen / Q000502:physiology; D013925:Thromboplastin / Q000096:biosynthesis* / Q000502:physiology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000627:therapeutic use*; D014471:Umbilical Veins
D000970:Antineoplastic Agents; D017077:Culture Media, Conditioned; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D013925:Thromboplastin