Influence of VEGF-R2 inhibition on MMP secretion and motility of microvascular human cerebral endothelial cells (HCEC).
作者： Sven Wagner , Tim Fueller , Vera Hummel , Peter Rieckmann , Joerg-Christian Tonn
关键词: Cell culture 、 Immunology 、 Motility 、 Endothelium 、 Cancer research 、 Umbilical vein 、 Neovascularization 、 Cell type 、 Biology 、 Endothelial stem cell 、 Cell
摘要: Neovascularization and invasion are key features of malignant gliomas. Matrix metalloproteinases (MMPs) supposed to play a major role mediating these processes. To analyze the expression patterns MMPs in microvascular human cerebral endothelial cells (HCEC), we isolated from normal brain microvessels. Characterization cellular origin was performed by immunostaining, using cell markers Ulex europaeus Agglutinin-1, von-Willebrand-Factor Glucose-transporter-1. Contamination other types tracked immunohistochemistry for GFAP (astrocytes), ASM (pericytes) CD68 (macrophages). Secretion evaluated ELISA zymography. determine whether HCEC show any difference MMP compared analyzed umbilical vein (HUVEC). decrease MMP-3 MMP-2 protein when treated with SU5416, VEGF-R2 (KDR/flk-1) inhibitor, whereas remained unchanged HUVEC. findings effect motility used three-dimensional co-culture assay avascular glioblastoma spheroids primary spheroids. Untreated controls showed both populations into each treatment co-cultures SU5416 resulted complete inhibition hence indicating that flk-1 related is critically involved this process can be studied assay. The results different effects anti-angiogenic on proteolytic properties two suggest neovascularization tumors vitro dependent surrounding type should therefore organ-specific cells.
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