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 |
|