Induction of vascular endothelial tubular morphogenesis by human glioma cells. A model system for tumor angiogenesis.

Abstract

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 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. (J.

Endothelial cell differentiation into capillary-like structures in response to tumour cell conditioned medium: a modified chemotaxis chamber assay

“…The blocking of the effects of Bl6F0 CM by anti-bFGF antibody in our assay could therefore be explained if bFGF was released by such yet undefined mechanisms. A similar effect of anti-bFGF antibodies on the conditioned media of glioma cell lines has been described (Abe et al, 1993).…”

“…Using this co-culture system, tubular morphogenesis by human omentum microvascular endothelial cells in type I collagen gels was shown to be induced by transforming growth factor alpha (TGF-x)-producing oesophageal tumour cells or keratinocytes . BAE cells also form capillary structures in type I collagen when co-cultured with human glioma cell lines (Abe et al, 1993); in this case a direct correlation between tubulogenesis of BAE cells and bFGF mRNA levels in glioma cells was demonstrated. These findings support the hypothesis that tumour cells directly control not only the proliferation and invasion steps, but also the differentiation of endothelial cells during tumour-induced angiogenesis.…”

“…basement membrane degradation (Murata et al, 1991), endothelial cell migration towards angiogenic factors (Augustin-Voss et al, 1992) or capillary formation within three-dimensional collagen gels (Pepper et al, 1992;Abe et al, 1993). This system reflects more closely the in vivo situation, and therefore we think that our tumourinduced angiogenesis model represents a valuable tool for the study of molecular interactions during the angiogenic process.…”

“…tumour-induced endothelial cell invasion and differentiation, we modified the chemotaxis chamber assay (Albini et al, 1987) in such a way that tumour cell CM induces the degradation of a Matrigel barrier by endothelial cells, their migration through it and their subsequent differentiation into CLS on a type I collagen layer. Although our tumour-induced angiogenesis assay shows homology to the co-culture system described by Abe et al (1993), there is a substantial difference between the models. In Abe's model, BAE cells seeded on a type I collagen gel migrate into it and differentiate into capillary structures; this tubulogenesis inside the gel requires a proteolytic degradation of type I collagen involving the activation of latent collagenase by tissue-type plasminogen activator (Sato et al, 1993).…”

Decorin suppresses tumor cell-mediated angiogenesis

“…It has been shown that bovine aortic endothelial cells form capillary-like structures in collagen type I when co-cultured with human glioma cells and that this process correlates with the production of FGF2 by the glioma cells (Abe et al, 1993). Thus, tumor cells appear to control, not only the proliferation and invasion steps, but also the differentiation of endothelial cells during tumor-induced angiogenesis.…”