CD10 as a novel marker of therapeutic resistance and cancer stem cells in head and neck squamous cell carcinoma.
CD10 as a novel marker of therapeutic resistance and cancer stem cells in head and neck squamous cell carcinoma.
复制标题
DOI：
10.1038/bjc.2014.289
复制
发表时间：
2014-07-29
影响因子：
8.8
通讯作者：
Inohara H
中科院分区：
文献类型：
--
作者：
Fukusumi T;Ishii H;Konno M;Yasui T;Nakahara S;Takenaka Y;Yamamoto Y;Nishikawa S;Kano Y;Ogawa H;Hasegawa S;Hamabe A;Haraguchi N;Doki Y;Mori M;Inohara H
癌症干细胞（CSC）是治疗失败的原因。然而，他们的鉴定和耐药的作用还没有很好地建立在头颈部鳞状细胞癌（HNSCC）。用顺铂或放射处理三种HNSCC细胞系（FaDu、Detroit 562和BICR 6）。细胞表面抗原分析LyoPlate，一种新的细胞表面抗原阵列。进一步比较顺铂耐药的Detroit 562细胞与其亲本细胞系在处理后高表达的抗原的表达水平。还检查了候选抗原与CSC性质（即球体形成和体内致瘤性）的关联。CD 10、CD 15 s、CD 146和CD 282在经处理的细胞系中上调，而CD 10的表达增加在顺铂耐药细胞系中突出。流式细胞仪介导的分离显示，CD 10阳性亚群更难治顺铂，氟尿嘧啶和放射比CD 10阴性亚群。它还显示出在体外形成球体和在体内形成肿瘤的能力增加。此外，CD 10阳性亚群表达CSC标志物OCT 3/4的水平高于CD 10阴性亚群。CD 10与HNSCC的治疗抗性和CSC样性质相关。CD 10可作为治疗难治性HNSCC的靶分子。
Cancer stem cells (CSCs) are responsible for treatment failure. However, their identification and roles in resistance are not well established in head and neck squamous cell carcinoma (HNSCC). Three HNSCC cell lines (FaDu, Detroit562 and BICR6) were treated with cisplatin or radiation. Cell surface antigens were analysed by LyoPlate, a novel cell surface antigen array. The expression levels of antigens highly expressed after treatments were further compared between cisplatin-resistant Detroit562 cells and its parental line. Association of the candidate antigen with CSCs properties, namely sphere formation and in vivo tumourigenicity, was also examined. CD10, CD15s, CD146 and CD282 were upregulated across the treated cell lines, while the increased expression of CD10 was prominent in the cisplatin-resistant cell line. Isolation mediated by FACS revealed that the CD10-positive subpopulation was more refractory to cisplatin, fluorouracil and radiation than the CD10-negative subpopulation. It also showed an increased ability to form spheres in vitro and tumours in vivo. Moreover, the CD10-positive subpopulation expressed the CSC marker OCT3/4 at a higher level than that in the CD10-negative subpopulation. CD10 is associated with therapeutic resistance and CSC-like properties of HNSCC. CD10 may serve as a target molecule in the treatment of refractory HNSCC.