趨化因子CCL5及其受體CCR5在乳腺癌進(jìn)展過(guò)程中的作用一直是個(gè)謎,。5月25日Cancer Research 雜志在線發(fā)表了Marco Velasco-Velazquez等人的研究論文闡明了其中的奧秘。
研究者通過(guò)對(duì)2254個(gè)人乳腺癌標(biāo)本的微陣列分析發(fā)現(xiàn)，在基底型和HER-2亞型的標(biāo)本中CCL5和CCR5表達(dá)升高,。表達(dá)CCR5的乳腺癌細(xì)胞亞群可響應(yīng)CCL5信號(hào),，產(chǎn)生功能性改變,。此外,，癌基因的轉(zhuǎn)化作用誘導(dǎo)CCR5的表達(dá)，而且表達(dá)功能性CCR5的癌細(xì)胞亞群也更具侵襲性,。CCR5拮抗劑Maraviroc或者Vicriviroc可降低基底型乳腺癌細(xì)胞在體外實(shí)驗(yàn)中的侵襲力,，但不影響細(xì)胞增殖和存活。Maraviroc還可降低小鼠乳腺癌模型中肺轉(zhuǎn)移的幾率,。
總之,，該研究證實(shí)了CCL5/CCR5在基底型乳腺癌侵襲力中的作用,，并且提示CCR5拮抗劑可作為輔助治療手段降低該亞型患者腫瘤轉(zhuǎn)移的風(fēng)險(xiǎn)。(生物谷Bioon.com)
doi:10.1016/j.cell.2011.10.017
CCR5 antagonist blocks metastasis of basal breast cancer cells
Marco Velasco-Velazquez, Xuanmao Jiao, Marisol De La Fuente et al.
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.
