Glioma cells under hypoxic conditions block the brain microvascular endothelial cell death induced by serum starvation.

作者: Yoshifumi Ueda , Takao Nakagawa , Toshihiko Kubota , Kazunori Ido , Kazufumi Sato

DOI: 10.1111/J.1471-4159.2005.03343.X

关键词:

摘要: Angiogenesis is one of essential components for the growth neoplasms, including malignant gliomas. However, tumor vascularization often poorly organized and marginally functional due to structural abnormalities, inducing regional or temporal hypoxic conditions nutritional shortages in tissues. We investigated how during angiogenesis migrating endothelial cells survive these reduced conditions. Human brain microvascular (HBMECs) underwent apoptosis necrosis after serum withdrawal. This cell death was blocked by recombinant VEGF protein culture medium U251 glioma exposed hypoxia (H-CM). Hypoxic treatment increased vascular factor (VEGF) alpha (TNF-alpha) expression cells. H-CM activated nuclear factor-kappaB (NFkappaB) gene antiapoptotic factors Bcl-2, Bcl-X(L), survivin X-chromosome-linked inhibitor (XIAP) The survival activity abolished two kinds inhibitors {Cyclopeptidic a receptor tyrosine kinase (4-[(4'-chloro-2'-fluoro) phenylamino]-6, 7-dimethoxyquinazoline)} NFkappaB (ALLN BAY 11-7082). These did not block activation induced On contrary, TNF-alpha antagonist WP9QY enhanced under serum-starved Taken together, our data suggest that both secretion from are necessary as they increase genes starvation. pathways may be mechanisms which maintained

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