APOPTOSIS OF HUMAN GLIOMA-CELLS IN-VITRO AND IN-VIVO INDUCED BY A NEUTRALIZING ANTIBODY AGAINST HUMAN BASIC FIBROBLAST GROWTH-FACTOR

Basic fibroblast growth factor (bFGF) is mitogenic to neuroectoderm- a nd mesoderm-derived cells and is a potent angiogenic factor. Abundant amounts of this factor and its receptor are detected in human glioma t issues and cells, and bFGF in glioma is thought to be involved in auto nomous cell growth as an autocrine growth factor. A neutralizing mouse monoclonal antibody (MAb) against bFGF, 3H3 MAb, has been shown to in hibit both in vitro and in vivo growth of human glioma cell lines. Thi s study shows that the human glioma cell lines U-87MG and U-251MG, whi ch express high levels oi bFGF and its receptor, can be induced to und ergo apoptosis when cultured with 3H3 MAb. It is also demonstrated tha t 3H3 MAb can cause apoptosis in the same glioma cells that were trans planted into nude mice. Furthermore, enforced overexpression of bcl-2 protein by gene transfection prevented 3H3 MAb-induced apoptosis of gl ioma cells. It is concluded that induction of apoptosis by tbe neutral izing antibody is a promising therapeutic strategy for glioma.