RRC ID 42681
著者 Chiba T, Kita K, Zheng YW, Yokosuka O, Saisho H, Iwama A, Nakauchi H, Taniguchi H.
タイトル Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties.
ジャーナル Hepatology
Abstract 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.
巻・号 44(1)
ページ 240-51
公開日 2006-7-1
DOI 10.1002/hep.21227
PMID 16799977
MeSH Apoptosis Carcinoma, Hepatocellular / genetics Carcinoma, Hepatocellular / metabolism Carcinoma, Hepatocellular / pathology* Cell Line, Tumor Flow Cytometry Gene Expression Regulation, Neoplastic Hepatocytes / pathology* Humans Immunohistochemistry In Vitro Techniques Keratins / genetics Keratins / metabolism Liver Neoplasms / genetics Liver Neoplasms / metabolism Liver Neoplasms / pathology* Neoplasm Transplantation Neoplastic Stem Cells / pathology* RNA, Neoplasm / genetics Reverse Transcriptase Polymerase Chain Reaction Transplantation, Heterologous alpha-Fetoproteins / genetics alpha-Fetoproteins / metabolism
IF 14.679
引用数 517
WOS 分野 GASTROENTEROLOGY & HEPATOLOGY
リソース情報
ヒト・動物細胞