趨化因子CCL5和其受體CCR5在乳腺癌進展中的作用仍不清楚,。在一項最新煙具中,，腫瘤領域研究人員對2,254人乳腺癌標本進行基因芯片分析后發(fā)現(xiàn)在HER-2基因亞型乳腺癌中，CCL5的表達及其受體CCR5時增加,，但CCR3表達不增加的,。
同時也發(fā)現(xiàn)表達CCR5人乳腺癌細胞系對CCL5有功能反應。在此種腫瘤亞型中,，癌基因會轉(zhuǎn)化誘導CCR5的表達,，而一點表達CCR5后，細胞侵襲能力增加了,。
在臨床前小鼠乳腺癌肺轉(zhuǎn)移模型中使用CCR5拮抗劑以阻斷受體CCR5的功能,，結(jié)果發(fā)現(xiàn)在不影響細胞增殖或活力的情況下能降低基底乳腺癌細胞的體外侵襲。
研究結(jié)果揭示了CCL5/CCR5對基底乳腺癌細胞侵襲生物學行為的關鍵作用,，CCR5拮抗劑可作為基底亞型乳腺癌患者的輔助治療藥物,，以減少轉(zhuǎn)移的風險。（生物谷：Bioon.com）
doi:10.1158/0008-5472.CAN-11-3917
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CCR5 Antagonist Blocks Metastasis of Basal Breast Cancer Cells
Marco Velasco-Velázquez1,2,4, Xuanmao Jiao1,2, Marisol De La Fuente4, et al.
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.
