The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Side population purified from hepatocellular carcinoma cells harbors cancer stem cell–like properties
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 × 103 SP cells were sufficient for tumor formation, whereas an injection of 1 × 106 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. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).
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Metadata
- Authors
- Chiba, T., Kita, K., Zheng, Y.-W., Yokosuka, O., Saisho, H., Iwama, A., Nakauchi, H., & Taniguchi, H.
- Venue
- Hepatology
- Published
- 2006-07
- Volume
- 44
- Issue
- 1
- Pages
- 240-251
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W2130976070
- Cited by
- 664
- References
- 46
- FWCI
- 21.08
- Type
- journal article
- Language
- en
- Open access
- closed
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- Chiba, T., Kita, K., Zheng, Y.-W., Yokosuka, O., Saisho, H., Iwama, A., Nakauchi, H., & Taniguchi, H. (2006). Side population purified from hepatocellular carcinoma cells harbors cancer stem cell–like properties. Hepatology. https://doi.org/10.1002/hep.21227
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