Chen Lingchao, Liu Xing, Zhang Hai-Yan, Du Wenzong, Qin Zhiyong, Yao Yu, Mao Ying, Zhou Liangfu
Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
Department of Neurosurgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Oncotarget. 2014 Aug 30;5(16):6576-83. doi: 10.18632/oncotarget.2134.
Human gliomas are characterized by their invasion of normal brain structures irrespective of their grade of malignancy. Tumor cell invasion share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. Here we report that the chemokine receptor CCR10 is highly expressed in human glioblastoma compared with control brain tissue. In vitro, signaling through CCL27-CCR10 mediates activation of p-Akt, and subsequently induces proliferation and invasive responses. Cell proliferation and invasion promoted by CCL27 were blocked by inhibition of p-Akt or CCR10. In vivo, down-regulation of CCR10 significantly impairs growth of glioma. Clinically, High CCR10 expression in GBM correlated with p-Akt, shorter overall survival and progression-free survival (P < 0.05). Together, these findings suggest that elevated CCR10 is a critical molecular event associated with gliomagenesis.
人类胶质瘤的特征是无论其恶性程度如何，都会侵袭正常脑结构。肿瘤细胞侵袭与白细胞迁移有许多相似之处，而白细胞迁移受趋化因子及其受体的严格调控。在此我们报告，与对照脑组织相比，趋化因子受体CCR10在人类胶质母细胞瘤中高度表达。在体外，通过CCL27-CCR10的信号传导介导p-Akt的激活，随后诱导增殖和侵袭反应。CCL27促进的细胞增殖和侵袭被p-Akt或CCR10的抑制所阻断。在体内，CCR10的下调显著损害胶质瘤的生长。临床上，胶质母细胞瘤中CCR10的高表达与p-Akt、较短的总生存期和无进展生存期相关（P<0.05）。这些发现共同表明，CCR10升高是与胶质瘤发生相关的关键分子事件。
