Chemokine C-X-C motif receptor 6 contributes to cell migration during hypoxia
Chemokine C-X-C motif receptor 6 contributes to cell migration during hypoxia
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DOI：
10.1016/j.canlet.2009.01.029
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发表时间：
2009-06-28
期刊：
影响因子：
9.7
通讯作者：
Zhang, Luyong
中科院分区：
文献类型：
--
作者：
Lin, Sensen;Sun, Li;Zhang, Luyong
趋化因子和趋化因子受体家族在肿瘤发生中起重要作用。尽管CXCR 4和CCR 7已被报道与癌症转移相关，但对其他趋化因子受体在癌症中的作用知之甚少。我们探讨了CXCR 6在缺氧诱导的细胞迁移中的地位。乳腺癌细胞和人脐静脉内皮细胞（HUVEC）表达CXCR 6，并表现出明显的趋化性迁移到CXCL 16。缺氧时CXCR 6 mRNA和蛋白显著积累。CXCR 6的过表达增加了细胞的迁移，而CXCR 6的敲低减弱了缺氧介导的细胞迁移和MMP-2的分泌。为了研究低氧条件下CXCR 6表达调控的可能机制，我们检测了HIF-1 α的表达，发现HIF-1 α参与了CXCR 6的调控。CXCR 6和HIF-1 α在乳腺癌淋巴结转移灶中高表达。我们的数据表明CXCR 6在缺氧期间显著促进细胞迁移。(C)2009爱思唯尔爱尔兰有限公司保留所有权利。
The chemokine and chemokine receptor families have important roles in tumorigenesis. Although CXCR4 and CCR7 have been reported to be associated with cancer metastasis, the role of other chemokine receptors in cancer is poorly understood. We explored the status of CXCR6 in hypoxia-induced cell migration. Breast cancer cells and human umbilical vein endothelial cells (HUVEC) expressed CXCR6, and showed appreciable chemotactic migration to CXCL16. Significant accumulation of CXCR6 mRNA and protein during hypoxia was observed. Overexpression of CXCR6 increased cell migration, and knockdown of CXCR6 attenuated hypoxia-mediated cell migration and MMP-2 secretion. To investigate possible mechanisms regulating CXCR6 expression during hypoxia, we detected the expression of HIFs and found that HIF-1 alpha was involved in CXCR6 regulation. CXCR6 and HIF-1 alpha were highly expressed in breast cancer lymph nodes metastases. Our data suggest CXCR6 contributes significantly to cell migration during hypoxia. (C) 2009 Elsevier Ireland Ltd. All rights reserved.