title: Hypoxia inducible factor-1 is involved in growth factor, glucocorticoid and hypoxia mediated regulation of vascular endothelial growth factor-A in human meningiomas.
abstract: In meningiomas, neovascularization through angiogenesis is essential for tumor expansion. As the vascular endothelial growth factor-A (VEGF-A) plays an outstanding role in this process, we have studied basal VEGF-A release and some aspects of its regulation in 46 meningiomas and in Ben-Men-1 cells in vitro. Among two putative VEGF-A stimulating growth factors tested, TGF-1β was more potent than TGF-α in enhancing VEGF-A secretion. Hypoxia-mimicking conditions induced by CoCl2 treatment also strongly increased VEGF-A secretion. The synthetic glucocorticoid dexamethasone (DEX) potently suppressed both basal and growth factor or CoCl2-induced VEGF-A release. All these effects were also seen in the Ben-Men-1 cell line in which studies on the role of HIF-1 in the regulation of VEGF-A showed that not only hypoxia but also the growth factors induced HIF-1α and DEX suppressed HIF-1α induction. Therefore, in Ben-Men-1 cells with HIF-1α knock-down the effects of hypoxia, growth factors and DEX on VEGF-A production were strongly impaired. This clearly indicates that HIF-1 not only regulates hypoxia-induced VEGF-A production but also mediates at least in part the effects of growth factors and DEX on VEGF-A synthesis and release. Our findings show the complexity of VEGF-A regulation in meningiomas and point to new options for the pharmacological treatment of these tumors.
authors: Department of Endocrinology, Max-Planck-Institute of Psychiatry, Kraepelinstr. 10, 80804, Munich, Germany.
authors: Y
authors: Y
authors: Wu
authors: K
authors: K
authors: Lucia
authors: M
authors: M
authors: Lange
authors: D
authors: D
authors: Kuhlen
authors: G K
authors: GK
authors: Stalla
authors: U
authors: U
authors: Renner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D015687:Cell Hypoxia / Q000502:physiology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003035:Cobalt; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008579:Meningioma / Q000188:drug therapy / Q000378:metabolism*; D008875:Middle Aged; D016211:Transforming Growth Factor alpha / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D051793:Hypoxia-Inducible Factor 1; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D003035:Cobalt; D003907:Dexamethasone; C018021:cobaltous chloride