CCR5 Antagonist Blocks Metastasis of Basal Breast Cancer Cells
CCR5 Antagonist Blocks Metastasis of Basal Breast Cancer Cells
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DOI：
10.1158/0008-5472.can-11-3917
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发表时间：
2012-08-01
期刊：
影响因子：
11.2
通讯作者：
Pestell, Richard G.
中科院分区：
文献类型：
--
作者：
Velasco-Velazquez, Marco;Jiao, Xuanmao;Pestell, Richard G.
趋化因子 CCL5 及其受体 CCR5 在乳腺癌进展中的作用仍不清楚。在这里，我们对 2,254 份人类乳腺癌样本进行了微阵列分析，发现在基础基因亚型和 HER-2 基因亚型中，CCL5 及其受体 CCR5 的表达增加，但 CCR3 的表达没有增加。发现表达 CCR5 的人类乳腺癌细胞系亚群表现出对 CCL5 的功能性反应。此外，癌基因转化诱导CCR5表达，表达功能性CCR5的细胞亚群也表现出侵袭性增加。 CCR5拮抗剂maraviroc或vicriviroc开发用于阻断CCR5 HIV辅助受体功能，在不影响细胞增殖或活力的情况下减少基底乳腺癌细胞的体外侵袭，并且maraviroc减少临床前乳腺癌小鼠模型中的肺转移。综上所述，我们的研究结果为 CCL5/CCR5 在基底乳腺癌细胞侵袭性中的关键作用提供了证据，并表明 CCR5 拮抗剂可用作辅助治疗，以降低基底乳腺癌亚型患者的转移风险。癌症研究； 72(15)； 3839-50。 (C) 2012 年 AACR。
The roles of the chemokine CCL5 and its receptor CCR5 in breast cancer progression remain unclear. Here, we conducted microarray analysis on 2,254 human breast cancer specimens and found increased expression of CCL5 and its receptor CCR5, but not CCR3, in the basal and HER-2 genetic subtypes. The subpopulation of human breast cancer cell lines found to express CCR5 displayed a functional response to CCL5. In addition, oncogene transformation induced CCR5 expression, and the subpopulation of cells that expressed functional CCR5 also displayed increased invasiveness. The CCR5 antagonists maraviroc or vicriviroc, developed to block CCR5 HIV coreceptor function, reduced in vitro invasion of basal breast cancer cells without affecting cell proliferation or viability, and maraviroc decreased pulmonary metastasis in a preclinical mouse model of breast cancer. Taken together, our findings provide evidence for the key role of CCL5/CCR5 in the invasiveness of basal breast cancer cells and suggest that CCR5 antagonists may be used as an adjuvant therapy to reduce the risk of metastasis in patients with the basal breast cancer subtype. Cancer Res; 72(15); 3839-50. (C) 2012 AACR.