Sphere-forming cell subpopulations with cancer stem cell properties in human hepatoma cell lines
Open Access
- 14 June 2011
- journal article
- Published by Springer Science and Business Media LLC in BMC Gastroenterology
- Vol. 11 (1), 71
- https://doi.org/10.1186/1471-230x-11-71
Abstract
Background Cancer stem cells (CSCs) are regarded as the cause of tumor formation and recurrence. The isolation and identification of CSCs could help to develop novel therapeutic strategies specifically targeting CSCs. Methods Human hepatoma cell lines were plated in stem cell conditioned culture system allowed for sphere forming. To evaluate the stemness characteristics of spheres, the self-renewal, proliferation, chemoresistance, tumorigenicity of the PLC/PRF/5 sphere-forming cells, and the expression levels of stem cell related proteins in the PLC/PRF/5 sphere-forming cells were assessed, comparing with the parental cells. The stem cell RT-PCR array was performed to further explore the biological properties of liver CSCs. Results The PLC/PRF/5, MHCC97H and HepG2 cells could form clonal nonadherent 3-D spheres and be serially passaged. The PLC/PRF/5 sphere-forming cells possessed a key criteria that define CSCs: persistent self-renewal, extensive proliferation, drug resistance, overexpression of liver CSCs related proteins (Oct3/4, OV6, EpCAM, CD133 and CD44). Even 500 sphere-forming cells were able to form tumors in NOD/SCID mice, and the tumor initiating capability was not decreased when spheres were passaged. Besides, downstream proteins DTX1 and Ep300 of the CSL (CBF1 in humans, Suppressor of hairless in Drosophila and LAG1 in C. elegans) -independent Notch signaling pathway were highly expressed in the spheres, and a gamma-secretase inhibitor MRK003 could significantly inhibit the sphere formation ability. Conclusions Nonadherent tumor spheres from hepatoma cell lines cultured in stem cell conditioned medium possess liver CSC properties, and the CSL-independent Notch signaling pathway may play a role in liver CSCs.Keywords
This publication has 42 references indexed in Scilit:
- CD13 is a therapeutic target in human liver cancer stem cellsJCI Insight, 2010
- Quantitative evaluation of DNA hypermethylation in malignant and benign breast tissue and fluidsInternational Journal of Cancer, 2009
- Hepatocellular Carcinoma Incidence, Mortality, and Survival Trends in the United States From 1975 to 2005Journal of Clinical Oncology, 2009
- Liver Cancer Stem CellsJournal of Clinical Oncology, 2008
- Growth of cancer cell lines under stem cell-like conditions has the potential to unveil therapeutic targetsExperimental Cell Research, 2008
- Identification and Characterization of Ovarian Cancer-Initiating Cells from Primary Human TumorsCancer Research, 2008
- Anchorage-independent culture maintains prostate stem cellsDevelopmental Biology, 2007
- Hepatocellular Carcinoma: Epidemiology and Molecular CarcinogenesisGastroenterology, 2007
- A Tumorigenic Subpopulation with Stem Cell Properties in MelanomasCancer Research, 2005
- Global cancer statistics in the year 2000The Lancet Oncology, 2001