Cui Feilun, Tang Huaming, Tan Jian, Hu Jianpeng
Department of Urology, Zhenjiang First People's Hospital, Zhenjiang 212002, China.
Aging (Albany NY). 2018 Nov 8;10(11):3273-3282. doi: 10.18632/aging.101631.
Spindle pole body component 25 (SPC25) is a component of NDC80 complex that controls spindle assembly checkpoint in the microtubule-binding domain of kinetochores. We recently showed that SPC25 is required for prostate cancer (PrC) cell proliferation and cell cycle progression, and here we investigated whether SPC25 may be a Cancer stem cell (CSC) marker in PrC. We found that the levels of SPC25 were higher in PrC samples than paired normal prostate tissue. The overall survival of PrC patients with high SPC25 was poorer than those with low SPC25. PrC cell lines were transduced with two vectors carrying a luciferase reporter and a mCherry fluorescent reporter under a cytomegalovirus promoter and a nuclear green fluorescent protein reporter under the control of a SPC25 promoter, respectively, to allow differentiating SPC25+ from SPC25- PrC cells by flow cytometry. Compared to SPC25- cells, SPC25+ cells formed significantly more tumor spheres in culture, appeared to be more resistant towards docetaxel-induced cell apoptosis, and generated larger tumors with higher frequency after serial adoptive transplantation. Thus, our data suggest that SPC25 may be highly expressed in the CSC-like cells in PrC and could be a promising target for effective treatment of PrC.
纺锤体极体成分25(SPC25)是NDC80复合物的一个成分,该复合物在动粒的微管结合结构域中控制纺锤体组装检查点。我们最近发现SPC25是前列腺癌(PrC)细胞增殖和细胞周期进程所必需的,在此我们研究了SPC25是否可能是PrC中的癌症干细胞(CSC)标志物。我们发现PrC样本中SPC25的水平高于配对的正常前列腺组织。SPC25水平高的PrC患者的总生存期比SPC25水平低的患者差。分别用两种载体转导PrC细胞系,一种载体携带在巨细胞病毒启动子控制下的荧光素酶报告基因和mCherry荧光报告基因,另一种载体携带在SPC25启动子控制下的核绿色荧光蛋白报告基因,以便通过流式细胞术区分SPC25+和SPC25-的PrC细胞。与SPC25-细胞相比,SPC25+细胞在培养中形成的肿瘤球明显更多,似乎对多西他赛诱导的细胞凋亡更具抗性,并且在连续过继移植后更频繁地产生更大的肿瘤。因此,我们的数据表明SPC25可能在PrC的CSC样细胞中高表达,并且可能是有效治疗PrC的一个有前景的靶点。