Tumor initiating potential of side population cells in human gastric cancer

Kazumasa Fukuda, Yoshirou Saikawa, Masaki Ohashi, Koshi Kumagai, Masaki Kitajima, Hideyuki Okano, Yumi Matsuzaki, Yuko Kitagawa

研究成果: Article査読

117 被引用数 (Scopus)

抄録

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 sub-population 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.

本文言語English
ページ(範囲)1201-1207
ページ数7
ジャーナルInternational journal of oncology
34
5
DOI
出版ステータスPublished - 2009

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究

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