美国密歇根大学研究人员4日说，动物实验显示，目前在临床试验中用于抑制器官移植排异反应的药物repertaxin可以精确打击癌症干细胞并阻止肿瘤扩散。
研究人员说，人体出现慢性炎症及组织损伤时会分泌白细胞介素－8蛋白，癌症患者接受化疗时，凋亡细胞也会分泌这种蛋白，这种蛋白能刺激癌症干细胞复制。试验显示，repertaxin可以抑制白细胞介素－8蛋白的受体CXCR1，从而对癌症干细胞实施精确打击。
研究人员以体内植入乳腺癌细胞的实验鼠为对象进行研究后发现，同时接受化疗和repertaxin治疗的实验鼠体内的癌症干细胞数量远低于只接受化疗的实验鼠，并且体内的肿瘤很少转移。
研究人员介绍说，癌症干细胞是促使肿瘤生长的“罪魁祸首”。它本身不会凋亡，还能在药物和化疗将癌症细胞杀死后促使肿瘤再生。
主持这项研究的马克斯·维夏表示，开发出针对癌症干细胞的有效疗法对改善癌症治疗效果至关重要，这一研究表明，类似repertaxin的药物或许可以提供精确打击癌症干细胞的方法。
这项研究成果4日发表在美国《临床检查杂志》网络版上。（生物谷Bioon.com）
生物谷推荐原始出处：
J Clin Invest. doi:10.1172/JCI39397.
CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts
Christophe Ginestier1,2, Suling Liu1, Mark E. Diebel1, Hasan Korkaya1, Ming Luo3, Marty Brown1, Julien Wicinski2, Olivier Cabaud2, Emmanuelle Charafe-Jauffret2, Daniel Birnbaum2, Jun-Lin Guan3, Gabriela Dontu1 and Max S. Wicha1
1University of Michigan Comprehensive Cancer Center, Department of Internal Medicine/Oncology, Ann Arbor, Michigan, USA.
2Centre de Recherche en Cancérologie de Marseille, Laboratoire d’Oncologie Moléculaire, UMR891 INSERM/Institut Paoli-Calmettes, Université de la Méditerranée, Marseille, France.
3Division of Molecular Medicine and Genetics and Cell and Developmental Biology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Recent evidence suggests that breast cancer and other solid tumors possess a rare population of cells capable of extensive self-renewal that contribute to metastasis and treatment resistance. We report here the development of a strategy to target these breast cancer stem cells (CSCs) through blockade of the IL-8 receptor CXCR1. CXCR1 blockade using either a CXCR1-specific blocking antibody or repertaxin, a small-molecule CXCR1 inhibitor, selectively depleted the CSC population in 2 human breast cancer cell lines in vitro. Furthermore, this was followed by the induction of massive apoptosis in the bulk tumor population via FASL/FAS signaling. The effects of CXCR1 blockade on CSC viability and on FASL production were mediated by the FAK/AKT/FOXO3A pathway. In addition, repertaxin was able to specifically target the CSC population in human breast cancer xenografts, retarding tumor growth and reducing metastasis. Our data therefore suggest that CXCR1 blockade may provide a novel means of targeting and eliminating breast CSCs.
