CXCL12 secreted from glioma stem cells regulates their proliferation
CXCL12 secreted from glioma stem cells regulates their proliferation
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DOI：
10.1007/s11060-014-1364-y
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发表时间：
2014-03-01
影响因子：
3.9
通讯作者：
Matsumura, Akira
中科院分区：
文献类型：
--
作者：
Uemae, Youji;Ishikawa, Eiichi;Matsumura, Akira
新的证据表明，神经胶质瘤干细胞 (GSC) 表达的趋化因子 CXCL12 及其受体 CXCR4 在肿瘤发生中发挥重要作用。为了为建立针对 CXCL12/CXCR4 通路的新疗法提供证据，我们研究了 GSC 分泌的 CXCL12 是否有助于其增殖并促进小鼠 GSC 的血管生成。使用管形成测定、RT-PCR 和增殖在体外模型以及体内同基因模型中评估有或没有 CXCL12 抑制剂的 GSC 的血管生成功能和增殖。在内皮培养中，GSC的形态和基因表达从干细胞样特征转变为内皮细胞样特征。内皮细胞样 GSC 中 CXCL12 表达增加。用 siRNA 或 shRNA 阻断 CXCL12 可显着抑制体外细胞增殖。用 shRNA 敲除 CXCL12 也能抑制体内肿瘤生长。另一方面，CXCL12/CXCR4 阻断既不影响体外管形成，也不影响体内血管生成。 GSC 分泌的 CXCL12（自分泌/旁分泌 CXCL12）调节其增殖，但可能不调节血管生成。
Emerging evidence suggests that the chemokine CXCL12 and its receptor CXCR4, which are expressed by glioma stem cells (GSCs), play an important role in tumorigenesis. To provide evidence for establishing a new therapy targeting the CXCL12/CXCR4 pathway, we investigated whether CXCL12 secreted from GSCs contributed to their proliferation and promoted angiogenesis in murine GSCs. Angiogenetic functions and proliferation of GSCs with or without CXCL12 inhibitors were evaluated in an in vitro model using tube formation assays, RT-PCR, and proliferation, as well as in an in vivo syngenic model. In endothelial culture, the morphology and gene expression of GSCs changed from stem cell-like characteristics to endothelial cell-like features. CXCL12 expression increased in endothelial cell-like GSCs. CXCL12 blockage with siRNA or shRNA markedly inhibited cell proliferation in vitro. CXCL12 knockdown with shRNA also inhibited tumor growth in vivo. On the other hand, CXCL12/CXCR4 blockage affected neither tube formation in vitro nor angiogenesis in vivo. The CXCL12 secreted from GSCs (autocrine/paracrine CXCL12) regulates their proliferation, but probably not angiogenesis.