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- W2605302195 abstract "AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA279 Bone marrow-derived endothelial progenitor cells (EPC) have been shown to play a critical role in tumor vasculogenesis. It is thought that EPC mobilize to tumors and support the formation of new blood vessels, which are essential for tumor growth and metastasis. Vascular endothelial growth inhibitor (VEGI; TNFSF15), a member of the tumor necrosis factor superfamily, is predominantly produced by endothelial cells (EC) and specifically targets EC to inhibit their proliferation and induce apoptosis. Here, we report that VEGI can inhibit the differentiation of hematopoietic stem cell (HSC) to EPC. We isolated Sca1+ cells from whole bone marrow from C57BL/6 mice and cultured them in EPC differentiating stimuli in the absence or presence of recombinant VEGI. Utilizing flow cytometry, we analyzed for occurrence of markers indicative of EPC, including CD133, c-kit, Tie-2, Flk-1, and VE-cadherin. We observed a significant inhibition of the expression of Tie-2, Flk-1 and VE-cadherin, but not that of CD133 or c-kit, on VEGI treated cells, indicating that these cells remain principally HSC. Consistently, the VEGI treated cells retained a morphology that more closely resembled the round, clustering HSC, whereas the untreated control cells gave a resemblance to EC within two weeks in culture. Functionally, HSC-derived cells cultured in the presence of VEGI exhibit a decreased capability of adhesion and migration. In addition, while the control cells were able to form tubular structures when plated on Matrigel, the VEGI treated cells lost such ability. These findings are consistent with the view that VEGI inhibits EPC differentiation from HSC under these experimental condition, suggesting that VEGI may take part in the modulation of post-natal vasculogenesis." @default.
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- W2605302195 date "2008-05-01" @default.
- W2605302195 modified "2023-10-02" @default.
- W2605302195 title "Inhibition of endothelial progenitor cell differentiation from hematopoietic stem cells by vascular endothelial growth inhibitor" @default.
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