A model system for tumor angiogenesis: Involvement of transforming growth factor-α in tube formation of human microvascular endothelial cells induced by esophageal cancer cells

Summary Tumor growth is dependent on angiogenesis, which is thought to be mediated through growth factors, such as transforming growth factor-α (TGF-α) and -β (TGF-β), 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 gets when these cells are co-cultured with tumor cells. Exogenously added TGF-α induced tube formation of HOME cells in collagen gel. In contrast, TGF-β inhibited the TGF-α-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-α and TGF-β mRNA, but the level of TGF-α mRNA in TE2 was found to be much lower than in TE1 cells. TE5 did not express either TGF-α or TGF-β. The tube formation of HOME cells 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-α-antibody, but not by anti-bFGF-antibody. The present study suggests that, in our model system, esophageal tumor angiogenesis is partly controlled by TGF-α, possibly through a paracrine pathway.