Universidad Nacional Autónoma de México, Facultad de Medicina , México DF , México.
Expert Opin Ther Targets. 2014 Nov;18(11):1265-75. doi: 10.1517/14728222.2014.949238. Epub 2014 Sep 26.
Chemokines play a crucial role in breast cancer tumorigenesis and progression. Recently, the chemokine (C-C motif) ligand 5 (CCL5), which can be secreted either by tumor cells or by mesenchymal stromal cells recruited to the tumor, has been identified as a key node in the bidirectional communication between breast cancer and normal cells.
In this review, the authors discuss the role of CCL5/chemokine receptor 5 (CCR5) axis in promoting breast cancer onset and progression. Interrogation of large clinical databases has demonstrated increased expression of the CCL5/CCR5 axis in specific subtypes of breast cancer. The activation of the receptor CCR5 in breast cancer cells controls their invasiveness serving as a driver for metastasis. Furthermore, the CCL5/CCR5 axis participates in the recruitment of specific immune cells into tumors, inducing local immunosuppression and favoring tumor progression.
The role of CCR5 in HIV infection led to the development of specific and potent CCR5 antagonists. The data reviewed here includes basic and translational studies that support the use of such CCR5 antagonists in breast cancer patients as adjuvant therapy to block the metastasis.
趋化因子在乳腺癌的发生和发展中起着至关重要的作用。最近,趋化因子(C-C 基序)配体 5(CCL5)已被确定为乳腺癌与正常细胞之间双向通讯的关键节点,它可以由肿瘤细胞或募集到肿瘤的间质基质细胞分泌。
在这篇综述中,作者讨论了 CCL5/趋化因子受体 5(CCR5)轴在促进乳腺癌发生和进展中的作用。对大型临床数据库的查询表明,特定亚型的乳腺癌中 CCL5/CCR5 轴的表达增加。受体 CCR5 在乳腺癌细胞中的激活控制着它们的侵袭性,成为转移的驱动因素。此外,CCL5/CCR5 轴参与特定免疫细胞招募到肿瘤中,诱导局部免疫抑制并促进肿瘤进展。
CCR5 在 HIV 感染中的作用导致了特异性和有效的 CCR5 拮抗剂的开发。这里综述的数据包括基础和转化研究,支持将这些 CCR5 拮抗剂作为辅助疗法用于乳腺癌患者,以阻断转移。