侧群细胞与肾癌肿瘤干细胞研究进展

Research progress of side population cells and renal cell carcinoma stem cells

目的总结国内外侧群细胞(side population,SP)及其在肾癌肿瘤干细胞中的研究进展。方法应用PubMed及中国知网期刊全文数据库检索系统,以"肿瘤干细胞、侧群细胞和肾癌"等为关键词,检索1996-01-2015-01的相关文献,共检索到英文文献660条,中文文献1 041条。纳入标准:1)肿瘤干细胞生物学特性;2)SP的表面标志和分选方法;3)肾癌肿瘤干细胞与SP相关性的研究。剔除标准:重复研究。最后纳入分析文献39篇。结果肿瘤干细胞是肿瘤发生、生长、转移和复发的根源,SP存在多种肿瘤细胞及肿瘤组织中,具有自我更新、多向分化和强大致瘤能力等干细胞的生物学特性,是肿瘤干细胞富集的亚群。利用SP细胞分选技术分离鉴定肿瘤干细胞及研究其生物学功能,将为肿瘤干细胞的研究提供新的方向。在对肾癌肿瘤干细胞的研究中发现SP细胞的分布,SP细胞表达的腺苷三磷酸转运蛋白G2(ATP binding cassette,ABCG2)能将多种化疗药物和外源性化学物质排出胞外,它的这种特性被认为与肾癌的多药耐药密切相关;肾癌SP细胞中乙醛脱氢酶1(aldehyde dehydrogenase 1,ALDH1)的表达明显高于非SP细胞,ALDH1阳性细胞在成球能力及致瘤能力上明显高于ALDH1阴性细胞。但是无论是ABCG2还是ALDH1都不是形成SP细胞表型的唯一原因。结论 SP可用于肾癌肿瘤干细胞的分选,但肾癌肿瘤干细胞的表面特征性标志仍需进一步研究。

OBJECTIVE To review the research progress of side population cells and renal cell carcinoma stem cells.METHODS Articles in PubMed and CNKI databases from January 1996 to January 2015 were retrieved by the key words＂cancer stem cells,side population cells and renal cell carcinoma＂.A total of 660 English articles and 1 041 Chinese articles were obtained.Inclusion criteria：1）biological characteristics of cancer stem cells 2）surface marker and sorting of side population cells 3）the relativity research between renal cell carcinoma stem cells and side population cells.Exclusion criteria：the repetitive research.Finally 39 articles were included for further analysis.RESULTS Cancer stem cells are the sources of cancer genesis,growth,metastasis and relapse.Side population cells lie in diverse cancer cells and tissues,which have the properties of stem cells,such as selfK-renewal,multidifferentiation,and higher tumorigenicity.Side population cells are stem cell-enriched populations.It will provide a new orientation for the research of cancer stem cells from isolation and analyzing the biologic function of side population cells.Side population cells are found in the research of renal cell carcinoma stem cells,The ATP binding cassette transporter G2 on side population cells could efflux chemotherapy drugs and chemical poisons,which are probably related to the drug-resistance of renal cell carcinoma.The expression of ALDH1 on side population cells are higher than that of non side population cells,ALDH1 positive cells have the stronger capability of growing tumor spheres and tumorigenicity compared with ALDH1 negative cells.But neither ALDH1 nor ABCG2is the sole cause of the formation of the side population cells phenotype.CONCLUSION The renal cell carcinoma stem cells can be identified and isolated by the side population cells,but the specific stem cell markers for renal cell carcinoma need to be further investigated.