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Expression of vascular endothelial growth factor-b in human astrocytoma

Institut de Pharmacologie Moléculaire et Cellulaire, 06560 Valbonne, France [J.C.G., A.L., C.F.]; Centre Antoine Lacassagne, Nice, France [J.G.]; Service de Neurochirurgie, Hôpital Pasteur, 30 Avenue de la Voie Romaine, 06002 Nice Cedex, France [P.P.]; and Laboratoire de Neuro-Oncologie, UER Médecine, 06102 Nice Cedex 2, France [A.D., M.C.]

² Address correspondence and reprint requests to Christian Frelin, Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UPR 411, 660 route des lucioles, 06560 Valbonne, France.

Abstract

Growth of human malignant gliomas is stringently dependent on an angiogenic process that probably involves vascular endothelial growth factor (VEGF). Expressions of mRNA coding for the different forms of VEGF were analyzed in surgical specimens from human astrocytomas. Low levels of placental growth factor (PGF) and VEGFC mRNA were observed in polymerase chain reaction, but not in Northern blot experiments. VEGF mRNA was found in some but not all grade and grade IV astrocytomas. VEGFB mRNA was observed in all tissue samples analyzed irrespective of the tumor grade. A new splice variant of VEGFB (VEGFB₁₅₅) that lacks exons 5 and 6 is described. Expressions of VEGF mRNA in cultured glioblastomas cells were upregulated by hypoxia, but the sensitivity of the cells to hypoxia was reduced as compared with normal rat astrocytes. VEGF expression was depressed by dexamethasone. Expressions of VEGFB mRNA were affected neither by hypoxia nor by dexamethasone. The results indicate a coexpression of VEGF mRNA and VEGFB mRNA in human astrocytomas. Expression of VEGFB is markedly different from that of VEGF. Possible roles of VEGFB as a cofactor for hypoxia-induced angiogenesis in human astrocytomas are discussed.

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