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

Biochem Biophys Res Commun. 1992 Aug 14;186(3):1471-9. doi: 10.1016/s0006-291x(05)81572-4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Northern
  • Cells, Cultured
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / drug effects
  • Esophageal Neoplasms / blood supply
  • Esophageal Neoplasms / physiopathology*
  • Fibroblast Growth Factor 2 / pharmacology
  • Humans
  • Microcirculation
  • Models, Biological
  • Neovascularization, Pathologic*
  • Omentum / blood supply
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recombinant Proteins / pharmacology
  • Transforming Growth Factor alpha / genetics
  • Transforming Growth Factor alpha / pharmacology
  • Transforming Growth Factor alpha / physiology*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta / physiology


  • RNA, Messenger
  • Recombinant Proteins
  • Transforming Growth Factor alpha
  • Transforming Growth Factor beta
  • Fibroblast Growth Factor 2