Cancer Res.: 趋化因子及受体CCL5/CCR5促进乳腺癌转移

趋化因子CCL5及其受体CCR5在乳腺癌进展过程中的作用一直是个谜。5月25日Cancer Research 杂志在线发表了Marco Velasco-Velazquez等人的研究论文阐明了其中的奥秘。

 

研究者通过对2254个人乳腺癌标本的微阵列分析发现，在基底型和HER-2亚型的标本中CCL5和CCR5表达升高。表达CCR5的乳腺癌细胞亚群可响应CCL5信号，产生功能性改变。此外，癌基因的转化作用诱导CCR5的表达，而且表达功能性CCR5的癌细胞亚群也更具侵袭性。CCR5拮抗剂Maraviroc或者Vicriviroc可降低基底型乳腺癌细胞在体外实验中的侵袭力，但不影响细胞增殖和存活。Maraviroc还可降低小鼠乳腺癌模型中肺转移的几率。

 

总之，该研究证实了CCL5/CCR5在基底型乳腺癌侵袭力中的作用，并且提示CCR5拮抗剂可作为辅助治疗手段降低该亚型患者肿瘤转移的风险。

doi:10.1016/j.cell.2011.10.017

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CCR5 antagonist blocks metastasis of basal breast cancer cells   Marco Velasco-Velazquez, Xuanmao Jiao, Marisol De La Fuente et al.    Abstract   The roles of the chemokine CCL5 and its receptor CCR5 in breast cancer progression remain unclear. Here we performed 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 co-receptor 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.