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Nature子刊:趋化因子受体CCR7促进乳腺癌肿瘤干细胞生长

摘要 : 近日,来自澳大利亚阿德莱德大学的研究人员在国际期刊oncogene在线发表了他们的最新发现,他们发现趋化因子受体CCR7能够调控乳腺癌中肿瘤干细胞的生长,提示我们CCR7或可成为治疗乳腺癌的一个潜在药物靶点。

 近日,来自澳大利亚阿德莱德大学的研究人员在国际期刊oncogene在线发表了他们的最新发现,他们发现趋化因子受体CCR7能够调控乳腺癌中肿瘤干细胞的生长,提示我们CCR7或可成为治疗乳腺癌的一个潜在药物靶点。

趋化因子受体CCR7广泛出现在乳腺癌病理生物学中。虽然最近一些研究表明CCR7高水平表达与晚期肿瘤分级和不良预后具有相关性,但关于其在乳腺癌中的特异性功能及参与的分子机制方面的体内研究仍非常有限。

为解决这些问题,研究人员构建了CCR7缺失的乳腺癌小鼠模型,通过观察发现CCR7缺失会导致乳腺癌发生明显迟滞同时伴随肿瘤负荷显著下降。通过对机制研究发现,在人类和小鼠肿瘤细胞中,CCR7能够通过调控具有干性特征的肿瘤细胞发挥功能。体内实验表明通过基因删除或药物阻断的方法抑制CCR7活性能够显著降低小鼠原发性乳腺癌干性细胞的数目,这为CCR7的促肿瘤生长功能提供了一个合理的机制解释。

这些结果揭示了CCR7在乳腺上皮瘤中的癌基因特性,为靶向肿瘤干细胞开发治疗干预手段提供了一个良好的作用靶点。

原文链接:The chemokine receptor CCR7 promotes mammary tumorigenesis through amplification of stem-like cells

The chemokine receptor CCR7 is widely implicated in breast cancer pathobiology. Although recent reports correlated high CCR7 levels with more advanced tumor grade and poor prognosis, limited in vivo data are available regarding its specific function in mammary gland neoplasia and the underlying mechanisms involved. To address these questions we generated a bigenic mouse model of breast cancer combined with CCR7 deletion, which revealed that CCR7 ablation results in a considerable delay in tumor onset as well as significantly reduced tumor burden. importantly, CCR7 was found to exert its function by regulating mammary cancer stem-like cells in both murine and human tumors. In vivo experiments showed that loss of CCR7 activity either through deletion or pharmacological antagonism significantly decreased functional pools of stem-like cells in mouse primary mammary tumors, providing a mechanistic explanation for the tumor-promoting role of this chemokine receptor. These data characterize the oncogenic properties of CCR7 in mammary epithelial neoplasia and point to a new route for therapeutic intervention to target evasive cancer stem cells.

来源: Oncogene 浏览次数:61

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