title: A model system for tumor angiogenesis: involvement of transforming growth factor-alpha in tube formation of human microvascular endothelial cells induced by esophageal cancer cells.
abstract: Tumor growth is dependent on angiogenesis, which is thought to be mediated through growth factors, such as transforming growth factor-alpha (TGF-alpha) and -beta (TGF-beta), epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF), produced by tumor cells. We have developed a model system for tumor angiogenesis in vitro: tube formation of human omentum microvascular endothelial (HOME) cells in type I collagen gels when these cells are co-cultured with tumor cells. Exogenously added TGF-alpha induced tube formation of HOME cells in collagen gel. In contrast, TGF-beta inhibited the TGF-alpha-induced tube formation of endothelial cells. We investigated whether tube formation could be induced in HOME cells in collagen gel when the HOME cells were co-cultured with three esophageal cancer cell lines, TE1, TE2, and TE5. TE1 and TE2 cells expressed both TGF-alpha and TGF-beta mRNA, but the level of TGF-alpha mRNA in TE2 was found to be much lower than in TE1 cells. TE5 did not express either TGF-alpha or TGF-beta. The tube formation of HOME cell was induced when they were co-cultured with TE1 cells, while both TE2 and TE5 cell lines induced tube formation at much lower rates than TE1. TE1-induced tube formation of HOME cells was specifically blocked by co-administration of anti-TGF-alpha-antibody, but not by anti-bFGF-antibody. The present study suggests that, in our model system, esophageal tumor angiogenesis is partly controlled by TGF-alpha, possibly through a paracrine pathway.
authors.affiliation: Department of Biochemistry, Oita Medical University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Okamura
authors.forename: A
authors.initials: A
authors.lastname: Morimoto
authors.forename: R
authors.initials: R
authors.lastname: Hamanaka
authors.forename: M
authors.initials: M
authors.lastname: Ono
authors.forename: K
authors.initials: K
authors.lastname: Kohno
authors.forename: Y
authors.initials: Y
authors.lastname: Uchida
authors.forename: M
authors.initials: M
authors.lastname: Kuwano
mesh_terms: D015152:Blotting, Northern; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000098:blood supply / Q000503:physiopathology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D008833:Microcirculation; D008954:Models, Biological; D009389:Neovascularization, Pathologic; D009852:Omentum / Q000098:blood supply; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000494:pharmacology / Q000502:physiology
chemical_list: D012333:RNA, Messenger; D011994:Recombinant Proteins; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2