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Cancer Res:CCR5拮抗剂阻断基底样乳腺癌细胞转移

来源:生物谷 2012-07-28 20:02

趋化因子CCL5和其受体CCR5在乳腺癌进展中的作用仍不清楚。在一项最新烟具中,肿瘤领域研究人员对2,254人乳腺癌标本进行基因芯片分析后发现在HER-2基因亚型乳腺癌中,CCL5的表达及其受体CCR5时增加,但CCR3表达不增加的。

同时也发现表达CCR5人乳腺癌细胞系对CCL5有功能反应。在此种肿瘤亚型中,癌基因会转化诱导CCR5的表达,而一点表达CCR5后,细胞侵袭能力增加了。

在临床前小鼠乳腺癌肺转移模型中使用CCR5拮抗剂以阻断受体CCR5的功能,结果发现在不影响细胞增殖或活力的情况下能降低基底乳腺癌细胞的体外侵袭。

研究结果揭示了CCL5/CCR5对基底乳腺癌细胞侵袭生物学行为的关键作用,CCR5拮抗剂可作为基底亚型乳腺癌患者的辅助治疗药物,以减少转移的风险。(生物谷:Bioon.com)

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.

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