INDUCTION OF VASCULAR ENDOTHELIAL TUBULAR MORPHOGENESIS BY HUMAN GLIOMA-CELLS - A MODEL SYSTEM FOR TUMOR ANGIOGENESIS

We have developed two different models of tumor angiogenesis by human brain tumors: one being tube formation by bovine aortic endothelial (BAE) cells cocultured with tumor cells in vitro, and other being in vivo angiogenesis in mice when tumor cells are transplanted into the dorsal sac. We investigated whether tube formation could be induced in BAE cells in type I collagen gel when these cells were cocultured with seven human glioma cell lines. Four of the seven glioma cell lines, which had high levels of basic fibroblast growth factor (BFGF) MRNA, induced tube formation by BAE cells. The tube formation was blocked by coadministration of anti-BFGF antibody. In vivo model system of tumor angiogenesis in mice, these four cell lines were highly angiogenic. In contrast, with the other three glioma cell lines, which had poor expression of BFGF, BAE cells showed no apparent tube formation. These three cell lines did not efficiently develop capillary networks in mice. The results demonstrated a correlative relationship in the tubulogenesis of BAE cells, BFGF MRNA levels and angiogenesis in mice. The present study with two model systems of tumor angiogenesis suggests that the angiogenesis of some human glioma cell lines is mediated by BFGF, possibly via paracrine control.