Institute of Pathology and Southwest Cancer Center, Third Military Medical University, Chongqing, China.
PLoS One. 2013;8(3):e57188. doi: 10.1371/journal.pone.0057188. Epub 2013 Mar 11.
Human glioblastomas (GBM) are thought to be initiated by glioma stem-like cells (GSLCs). GSLCs also participate in tumor neovascularization by transdifferentiating into vascular endothelial cells. Here, we report a critical role of GSLCs in the formation of vasculogenic mimicry (VM), which defines channels lined by tumor cells to supply nutrients to early growing tumors and tumor initiation. GSLCs preferentially expressed vascular endothelial growth factor receptor-2 (VEGFR-2) that upon activation by VEGF, mediated chemotaxis, tubule formation and increased expression of critical VM markers by GSLCs. Knockdown of VEGFR-2 in GSLCs by shRNA markedly reduced their capacity of self-renewal, forming tubules, initiating xenograft tumors, promoting vascularization and the establishment of VM. Our study demonstrates VEGFR-2 as an essential molecule to sustain the "stemness" of GSLCs, their capacity to initiate tumor vasculature, and direct initiation of tumor.
人胶质母细胞瘤（GBM）被认为是由神经胶质瘤干细胞（GSLCs）引发的。GSLCs 还通过向血管内皮细胞转分化参与肿瘤新生血管形成。在这里，我们报告了 GSLCs 在血管生成拟态（VM）形成中的关键作用，VM 定义了由肿瘤细胞排列的通道，为早期生长的肿瘤和肿瘤起始提供营养。GSLCs 优先表达血管内皮生长因子受体-2（VEGFR-2），VEGF 激活 VEGFR-2 后，介导 GSLCs 的趋化性、小管形成和关键 VM 标志物的表达增加。通过 shRNA 敲低 GSLCs 中的 VEGFR-2 ，显著降低了它们的自我更新能力、形成小管、启动异种移植物肿瘤、促进血管生成和建立 VM 的能力。我们的研究表明，VEGFR-2 是维持 GSLCs“干性”、启动肿瘤血管生成和直接启动肿瘤的必需分子。
