Fukuda Kazumasa, Saikawa Yoshiro, Ohashi Masaki, Kumagai Koshi, Kitajima Masaki, Okano Hideyuki, Matsuzaki Yumi, Kitagawa Yuko
Department of Surgery, School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan.
Int J Oncol. 2009 May;34(5):1201-7.
Side population (SP) cells are a small subpopulation of cells with enriched source of gastric tumor-initiating cells (TICs) with stem-like cell property that are characterized by high efflux ability of Hoechst 33342 dye, reflecting high expression of several subtypes of the ATP-binding cassette transporter family that is characteristic of stem cells. The present study is the first to discover and characterize SP cells within gastric cancer (GC) tumors. In this study, human GC cell lines (MKN45, KATOIII, MKN74, MKN28 and MKN1) were analyzed using flow cytometry for SP cell isolation, and all GC cell lines showed a distinct fraction of SP cells, ranging from 0.02+/-0.001 to 1.93+/-0.16%. Among these cell lines, MKN45 cultures possessed the highest percentage of SP cells. Using MKN45 cells, we demonstrated stem cell-like characteristics of SP cells of the cell lines as a possible subpopulation with enriched TICs, as indicated by ABC transporter gene expression (MDR1 and BCPR1), chemo-resistance and tumorigenicity in vivo. In addition, we report the first identification and isolation of SP cells from clinical GC tissues as well as human GC cell lines. These SP cells demonstrate higher tumorigenicity in vivo than does the overall cell population in the parent tissue. In conclusion, we demonstrate that solid tumor tissue such as human GC contains TICs, with the existence of heterogeneity and distinct hierarchy in malignancy, suggesting the future possibility of a novel therapeutic tool targeting TICs for overcoming this malignant disease.
侧群（SP）细胞是具有丰富胃癌起始细胞（TICs）来源的一小部分细胞亚群，这些起始细胞具有干细胞样特性，其特征是对Hoechst 33342染料具有高外排能力，这反映了ATP结合盒转运蛋白家族几种亚型的高表达，而这是干细胞的特征。本研究首次发现并鉴定了胃癌（GC）肿瘤中的SP细胞。在本研究中，使用流式细胞术分析人GC细胞系（MKN45、KATOIII、MKN74、MKN28和MKN1）以分离SP细胞，所有GC细胞系均显示出不同比例的SP细胞，范围为0.02±0.001%至1.93±0.16%。在这些细胞系中，MKN45培养物中SP细胞的百分比最高。利用MKN45细胞，我们证明了细胞系中SP细胞的干细胞样特性，它们可能是富含TICs的亚群，ABC转运蛋白基因表达（MDR1和BCPR1）、化学抗性和体内致瘤性均表明了这一点。此外，我们首次报道了从临床GC组织以及人GC细胞系中鉴定和分离出SP细胞。这些SP细胞在体内显示出比亲本组织中的总体细胞群更高的致瘤性。总之，我们证明了诸如人GC之类的实体瘤组织中含有TICs，在恶性程度上存在异质性和明显的层次结构，这表明未来有可能开发一种针对TICs的新型治疗工具来攻克这种恶性疾病。
