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

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. © 1992 Academic Press, Inc.