美國密歇根大學(xué)研究人員4日說，動物實(shí)驗(yàn)顯示,，目前在臨床試驗(yàn)中用于抑制器官移植排異反應(yīng)的藥物repertaxin可以精確打擊癌癥干細(xì)胞并阻止腫瘤擴(kuò)散,。
研究人員說，人體出現(xiàn)慢性炎癥及組織損傷時會分泌白細(xì)胞介素－8蛋白,，癌癥患者接受化療時,，凋亡細(xì)胞也會分泌這種蛋白，這種蛋白能刺激癌癥干細(xì)胞復(fù)制,。試驗(yàn)顯示,，repertaxin可以抑制白細(xì)胞介素－8蛋白的受體CXCR1，從而對癌癥干細(xì)胞實(shí)施精確打擊,。
研究人員以體內(nèi)植入乳腺癌細(xì)胞的實(shí)驗(yàn)鼠為對象進(jìn)行研究后發(fā)現(xiàn),，同時接受化療和repertaxin治療的實(shí)驗(yàn)鼠體內(nèi)的癌癥干細(xì)胞數(shù)量遠(yuǎn)低于只接受化療的實(shí)驗(yàn)鼠，并且體內(nèi)的腫瘤很少轉(zhuǎn)移,。
研究人員介紹說,，癌癥干細(xì)胞是促使腫瘤生長的“罪魁禍?zhǔn)?rdquo;。它本身不會凋亡,，還能在藥物和化療將癌癥細(xì)胞殺死后促使腫瘤再生,。
主持這項(xiàng)研究的馬克斯·維夏表示，開發(fā)出針對癌癥干細(xì)胞的有效療法對改善癌癥治療效果至關(guān)重要,，這一研究表明,，類似repertaxin的藥物或許可以提供精確打擊癌癥干細(xì)胞的方法。
這項(xiàng)研究成果4日發(fā)表在美國《臨床檢查雜志》網(wǎng)絡(luò)版上,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
