Li Yiying, Chen Tong, Zhu Jie, Zhang Haiyan, Jiang Hua, Sun Hong
Department of Gynecology, Obstetrics & Gynecology Hospital, Fudan University, Shanghai 200011, China; Department of Gynecology, The First Affiliated Hospital, Nan Chang University, Nanchang 330006, China.
Department of Hematology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Biochem Biophys Res Commun. 2018 Jan 1;495(1):1081-1088. doi: 10.1016/j.bbrc.2017.11.117. Epub 2017 Nov 21.
Epithelial ovarian cancer (EOC) is highly metastatic and current therapeutics are unsatisfactory. Cancer stem/stem-like cells (CSCs/CSCLs) represent a rare population of undifferentiated oncogenic cells responsible for tumor initiation and maintenance. We identified ovarian cancer ALDH (aldehyde dehydrogenase) population could perform not only strengthened CSCLs properties embodied in colony-formation, CSCs-markers expression, and tumorigenesis in vivo, but also a greater invasive capacity with advanced EMT progress and anti-apoptosis compared with ALDH cells. Furthermore, both the stemness and aggressive features, along with ALDH percentages were in positive association with the invasiveness of cell lines for sorting, indicating the promotive role of ALDH CSCLs in EOC neoplasia and metastasis, since the whole tumor was derived from the CSCLs with hyperactive self-renewal and aggression. Collectively, this study illustrates the interplay between ALDH CSCLs and EOC invasion, and offers a novel application target for the EOC oncotherapy.
上皮性卵巢癌(EOC)具有高度转移性,目前的治疗方法并不令人满意。癌症干细胞/干细胞样细胞(CSCs/CSCLs)是一种罕见的未分化致癌细胞群体,负责肿瘤的起始和维持。我们发现,卵巢癌ALDH(醛脱氢酶)群体不仅具有增强的CSCLs特性,体现在集落形成、CSCs标志物表达和体内肿瘤发生方面,而且与ALDH细胞相比,具有更强的侵袭能力,伴有更高级的上皮-间质转化进程和抗凋亡能力。此外,干性和侵袭性特征以及ALDH百分比与分选的细胞系侵袭性呈正相关,这表明ALDH CSCLs在EOC肿瘤形成和转移中具有促进作用,因为整个肿瘤源自具有高度活跃自我更新和侵袭能力的CSCLs。总体而言,本研究阐明了ALDH CSCLs与EOC侵袭之间的相互作用,并为EOC肿瘤治疗提供了一个新的应用靶点。