title: Regulation of angiogenesis in human hepatomas: possible involvement of p53-inducible inhibitor of vascular endothelial cell proliferation.
abstract: Mechanisms regulating angiogenesis in human hepatomas were analyzed. Huh7 hepatoma cells transplanted into athymic mice formed highly vascularized reddish tumors with abundant microvessels, while angiogenesis by PLC/PRF/5 hepatoma cells was less remarkable. However, the production of angiogenesis stimulators such as VEGF and IL6 by Huh7 cells was much less than by PLC/PRF/5 cells. In addition, the production of angiogenesis inhibitor TSP-1 by Huh7 cells was greater than by PLC/PRF/5 cells. Therefore, the difference in angiogenesis between these two hepatomas was not explained by the production of these known angiogenesis regulators. On the other hand, PLC/PRF/5 cells but not Huh7 cells secreted an inhibitor of the proliferation of vascular endothelial cells, which was enhanced by p53-gene transfer. These results suggest that the production of this p53-inducible angiogenesis inhibitor is responsible, at least partly, for the regulation of angiogenesis in human hepatomas.
authors.affiliation: First Department of Medicine, Faculty of Medicine, The University of Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Tsukamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Kaneko
authors.forename: T
authors.initials: T
authors.lastname: Yoshida
authors.forename: M
authors.initials: M
authors.lastname: Ichinose
authors.forename: S
authors.initials: S
authors.lastname: Kimura
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001835:Body Weight; D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003510:Cyclohexanes; D016207:Cytokines / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018014:Gene Transfer Techniques; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000494:pharmacology; D019700:Thrombospondin 1 / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*
chemical_list: D000903:Antibiotics, Antineoplastic; D017077:Culture Media, Conditioned; D003510:Cyclohexanes; D016207:Cytokines; D012717:Sesquiterpenes; D019700:Thrombospondin 1; D016159:Tumor Suppressor Protein p53; D000077609:O-(Chloroacetylcarbamoyl)fumagillol