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- and mesoderm-derived cells and is a potent angiogenic factor. Abundant amounts of this factor and its receptor are detected in human glioma tissues and cells, and bFGF in glioma is thought to be involved in autonomous cell growth as an autocrine growth factor. A neutralizing mouse monoclonal antibody (MAb) against bFGF, 3H3 MAb, has been shown to inhibit both in vitro and in vivo growth of human glioma cell lines. This study shows that the human glioma cell lines U-87MG and U-251MG, which express high levels of bFGF and its receptor, can be induced to undergo apoptosis when cultured with 3H3 MAb. It is also demonstrated that 3H3 MAb can cause apoptosis in the same glioma cells that were transplanted into nude mice. Furthermore, enforced overexpression of bcl-2 protein by gene transfection prevented 3H3 MAb-induced apoptosis of glioma cells. It is concluded that induction of apoptosis by the neutralizing antibody is a promising therapeutic strategy for glioma.
Murai
N
N
Department of Neurosurgery, Graduate School of Medicine, Institute for Viral Research, Kyoto University, Japan.
Ueba
T
T
Takahashi
J A
JA
Yang
H Q
HQ
Kikuchi
H
H
Hiai
H
H
Hatanaka
M
M
Fukumoto
M
M
D000906:Antibodies / Q000494:pharmacology*; D017209:Apoptosis; D001932:Brain Neoplasms / Q000276:immunology / Q000473:pathology*; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression; D005910:Glioma / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D009500:Neutralization Tests; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
D000906:Antibodies; D019253:Proto-Oncogene Proteins c-bcl-2; D016222:Fibroblast Growth Factor 2