Strong expression of chemokine receptor CXCR4 by renal cell carcinoma cells correlates with metastasis
Strong expression of chemokine receptor CXCR4 by renal cell carcinoma cells correlates with metastasis
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DOI：
10.1007/s10585-009-9294-3
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发表时间：
2009-12-01
影响因子：
4
通讯作者：
Sun, Yinghao
中科院分区：
文献类型：
--
作者：
Wang, Linhui;Wang, Liang;Sun, Yinghao
趋化因子受体CXCR4参与多种肿瘤的转移。最近的证据表明，CXCR4可能也参与了肾癌的转移。采用免疫组织化学方法检测CXCR4在原发癌、转移癌组织和正常组织中的表达。我们进一步研究了体外培养的肾癌细胞对CXCL12刺激的迁移反应。我们还用共聚焦显微镜研究了CXCL12对肾癌细胞CXCR4亚细胞定位的影响。我们观察到CXCR4在肾癌转移灶中的表达比例最高，而在肾癌和正常肾组织中的表达最低。我们进一步发现，CXCR4在原发肾细胞癌中主要定位于细胞膜，在转移性肾细胞癌中主要定位于细胞质。此外，我们还发现，在其配体CXCL12的刺激下，CXCR4从细胞膜转移到细胞质中。肾细胞癌的转移与CXCR4的高表达有关，CXCR4与其配体CXCL12的相互作用导致CXCR4从细胞膜内化。这些发现提示CXCR4-CXCL12轴与肾癌的转移有关。
The chemokine receptor CXCR4 is involved in the metastasis of many cancers. Recent evidence suggests that CXCR4 may be also involved in the metastasis of renal cell carcinoma. We analyzed the expression of CXCR4 in primary carcinomas, metastatic tissues and normal tissues using immunohistochemistry. We further investigated the migration of renal carcinoma cells in response to stimulation by CXCL12 in vitro. We also studied the subcellular localization of CXCR4 in renal cell carcinoma cells in response to CXCL12 by confocal microscopy. We observed the highest percentage of CXCR4 expression in renal cell carcinoma metastases compared with that in renal cell carcinomas and normal renal tissues. We further found that CXCR4 was localized predominantly in the membrane in primary renal cell carcinomas and predominantly in the cytoplasm in renal cell carcinoma metastases. Moreover, we found that CXCR4 was translocated from the cytoplasmic membrane to the cytoplasm upon stimulation by its ligand CXCL12. Renal cell carcinoma metastasis was associated with higher expression of CXCR4 and interaction of CXCR4 and its ligand CXCL12 resulted in the internalization of CXCR4 from the cytoplasmic membrane. These findings implicate the CXCR4-CXCL12 axis in the metastasis of renal cell carcinoma.