Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties
Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties
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DOI：
10.1002/hep.21227
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发表时间：
2006-07-01
期刊：
影响因子：
13.5
通讯作者：
Taniguchi, Hideki
中科院分区：
文献类型：
--
作者：
Chiba, Tetsuhiro;Kita, Kaoru;Taniguchi, Hideki
干细胞生物学的最新进展使我们能够识别实体肿瘤中的癌症干细胞以及正常实体器官中的假定干细胞。在这项研究中，我们应用侧群（SP）细胞分析和分选建立肝细胞癌（HCC）细胞系，以检测作为癌症干细胞的亚群，并阐明其在肿瘤发生中的作用。在所分析的四种细胞系中，在Huh 7（0.25%）和PLC/PRF/5（0.80%）中检测到SP细胞，而在HepG 2和Huh 6细胞中未检测到SP细胞。与非SP细胞相比，SP细胞表现出较高的增殖潜力和抗凋亡特性。免疫细胞化学检查显示SP组分含有大量的细胞，呈现肝细胞和胆管细胞谱系的特征。非肥胖糖尿病/严重联合免疫缺陷（NOD/SCID）异种移植实验表明，只有1 × 10（3）SP细胞足以形成肿瘤，而注射1 × 10（6）非SP细胞不会引发肿瘤。对SP细胞源性肿瘤的再分析表明，SP细胞产生SP和非SP细胞，并且在连续移植中仅在SP细胞中维持肿瘤起始潜能。微阵列分析区分SP和非SP细胞之间的差异基因表达谱，和一些所谓的“干细胞基因”在HCC细胞中的SP细胞上调。总之，我们提出，少数人口，检测为SP细胞在肝癌细胞，具有极端的致瘤潜力，并提供异质性的癌症干细胞系统的特点是不同的层次结构。
Recent advances in stem cell biology enable us to identify cancer stem cells in solid tumors as well as putative stem cells in normal solid organs. In this study, we applied side population (SP) cell analysis and sorting to established hepatocellular carcinoma (HCC) cell lines to detect subpopulations that function as cancer stem cells and to elucidate their roles in tumorigenesis. Among four cell lines analyzed, SP cells were detected in Huh7 (0.25%) and PLC/PRF/5 cells (0.80%), but not in HepG2 and Huh6 cells. SP cells demonstrated high proliferative potential and anti-apoptotic properties compared with those of non-SP cells. Immunocytochemistry examination showed that SP fractions contain a large number of cells presenting characteristics of both hepatocyte and cholangiocyte lineages. Non-obese diabetic/severe combined immunodeficiency (NOD/SCID) xenograft transplant experiments showed that only 1 X 10(3)SP cells were sufficient for tumor formation, whereas an injection of 1 X 10(6) non-SP cells did not initiate tumors. Re-analysis of SP cell-derived tumors showed that SP cells generated both SP and non-SP cells and tumor-initiating potential was maintained only in SP cells in serial transplantation. Microarray analysis discriminated a differential gene expression profile between SP and non-SP cells, and several so-called "stemness genes" were upregulated in SP cells in HCC cells. In conclusion, we propose that a minority population, detected as SP cells in HCC cells, possess extreme tumorigenic potential and provide heterogeneity to the cancer stem cell system characterized by distinct hierarchy.