胶质母细胞瘤干细胞通过激活一种G蛋白偶联的甲酰肽受体FPR来产生血管内皮生长因子。
Glioblastoma stem cells produce vascular endothelial growth factor by activation of a G-protein coupled formylpeptide receptor FPR.
作者信息
Yao X-H, Ping Y-F, Chen J-H, Xu C-P, Chen D-L, Zhang R, Wang J M, Bian X-W
机构信息
Institute of Pathology, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.
出版信息
J Pathol. 2008 Aug;215(4):369-76. doi: 10.1002/path.2356.
Glioma stem cells (GSCs), or stem cell-like glioma cells, isolated from malignant glioma cell lines, were capable of producing vascular endothelial growth factor (VEGF). However, the exact role of such tumour cells in angiogenesis remains unknown. In this study, we isolated a small proportion of CD133+ GSCs from the human glioblastoma cell line U87 and found that these GSCs possessed multipotent differentiation potential and released high levels of VEGF as compared with CD133(-) tumour cells. The CD133+ GSCs also formed larger xenograft tumours that contained higher VEGF immunoreactivity and denser microvessels. Moreover, GSCs expressed a functional G protein-coupled formylpeptide receptor FPR, which was activated by a chemotactic peptide ligand, N-formylmethionyl-leucyl-phenylalanine (fMLF), to mediate calcium flux and the production of VEGF by GSCs. Our results indicate that FPR expressed by human GSCs may play an important role in glioma angiogenesis.
从恶性胶质瘤细胞系中分离出的胶质瘤干细胞（GSCs），即干细胞样胶质瘤细胞，能够产生血管内皮生长因子（VEGF）。然而，这类肿瘤细胞在血管生成中的确切作用仍不清楚。在本研究中，我们从人胶质母细胞瘤细胞系U87中分离出一小部分CD133 + GSCs，发现这些GSCs具有多能分化潜能，并且与CD133（ - ）肿瘤细胞相比，能释放高水平的VEGF。CD133 + GSCs还形成了更大的异种移植肿瘤，其中VEGF免疫反应性更高，微血管更密集。此外，GSCs表达一种功能性G蛋白偶联的甲酰肽受体FPR，它被趋化肽配体N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（fMLF）激活，以介导钙流和GSCs产生VEGF。我们的结果表明，人GSCs表达的FPR可能在胶质瘤血管生成中起重要作用。
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