Vascular permeability factor: a tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration.
Systemic infusion of low concentrations of tumor necrosis factor/cachectin (TNF) into mice that bear TNF-sensitive tumors leads to activation of coagulation, fibrin formation, and occlusive thrombosis exclusively within the tumor vascular bed. To identify mechanisms underlying the localization of this vascular procoagulant response, a tumor-derived polypeptide has been purified to homogeneity from supernatants of murine methylcholanthrene A-induced fibrosarcomas that induces endothelial tissue factor synthesis and expression (half-maximal response at approximately 300 pM), and augments the procoagulant response to TNF in a synergistic fashion. This tumor-derived polypeptide was identified as the murine homologue of vascular permeability factor (VPF) based on similar mobility on SDS-PAGE, an homologous NH2-terminal amino acid sequence, and recognition by a monospecific antibody to guinea pig VPF. In addition, VPF was shown to induce monocyte activation, as evidenced by expression of tissue factor. Finally, VPF was shown to induce monocyte chemotaxis across collagen membranes and endothelial cell monolayers. Taken together, these results indicate that VPF can modulate the coagulant properties of endothelium and monocytes, and can promote monocyte migration into the tumor bed. This suggests one mechanism through which tumor-derived mediators can alter properties of the vessel wall.
Clauss
M
M
Department of Physiology, Columbia University, College of Physicians and Surgeons, New York, New York 10032.
Gerlach
M
M
Gerlach
H
H
Brett
J
J
Wang
F
F
Familletti
P C
PC
Pan
Y C
YC
Olander
J V
JV
Connolly
D T
DT
Stern
D
D
D000595:Amino Acid Sequence; D000818:Animals; D001779:Blood Coagulation Factors / Q000096:biosynthesis*; D002460:Cell Line; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D003470:Culture Media; D016228:Endothelial Growth Factors / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006168:Guinea Pigs; D006801:Humans; D007106:Immune Sera; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology*; D008222:Lymphokines / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D012516:Osteosarcoma; D011994:Recombinant Proteins / Q000494:pharmacology; D012689:Sequence Homology, Nucleic Acid; D013925:Thromboplastin; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D001779:Blood Coagulation Factors; D003470:Culture Media; D016228:Endothelial Growth Factors; D007106:Immune Sera; D008222:Lymphokines; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C053675:endothelial cell procoagulant activity; C045071:leukocyte procoagulant activity; D013925:Thromboplastin