EpCAM-positive hepatocellular carcinoma cells are tumor initiating cells with stem/progenitor cell features
By T. Yamashita, Junfang Ji, A. Budhu, M. Forgues, Wen Yang, Hong-Yang Wang, H. Jia, Q. Ye, L. Qin, E. Wauthier and 6 more. Gastroenterology, 2008
1,175 citations recorded by the source corpus.
Background & Aims Cancer progression/metastases and embryonic development share many properties including cellular plasticity, dynamic cell motility, and integral interaction with the microenvironment. We hypothesized that the heterogeneous nature of hepatocellular carcinoma (HCC) may be, in part, due to the presence of hepatic cancer cells with stem/progenitor features. Methods Gene expression profiling and immunohistochemistry analyses were used to analyze 235 tumor specimens derived from two recently identified HCC subtypes (EpCAM+ AFP+ HCC and EpCAM− AFP− HCC). These subtypes differed in their expression of alpha-fetoprotein (AFP), a molecule produced in the developing embryo, and EpCAM, a cell surface hepatic stem cell marker. Fluorescence-activated cell sorting (FACS) was used to isolate EpCAM+ HCC cells, which were tested for hepatic stem/progenitor cell properties. Results Gene expression and pathway analyses revealed that the EpCAM+ AFP+ HCC subtype had features of hepatic stem/progenitor cells. Indeed, the FACS-isolated EpCAM+ HCC cells displayed hepatic cancer stem cell-like traits including the abilities to self-renew and differentiate. Moreover, these cells were capable of initiating highly invasive HCC in NOD/SCID mice. Activation of Wnt/β-catenin signaling enriched the EpCAM+ cell population, while RNA interference-based blockage of EpCAM, a Wnt/β-catenin signaling target, attenuated the activities of these cells. Conclusions Taken together, our results suggest that HCC growth and invasiveness is dictated by a subset of EpCAM+ cells, opening a new avenue for HCC cancer cell eradication by targeting Wnt/β-catenin signaling components such as EpCAM.
Subfields: Hepatology, Oncology
View Paper: https://www.semanticscholar.org/paper/372bd7113dd84d0960a1c5bd542097b1ecadc2ec
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Citations in the corpus
- Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver. (2012, positive): “Such genes include components of insulin-like growth factor 2 ( Igf2 ), Ras , and β -catenin ( Ctnnb1 ) signaling pathways (Supplemental Figure 4A), as well as other genes known to play a role in HCC such as Epcam (21), c-Myc (22), Mapre1 (23), and Rhoa (24).”
- EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer (2010, background): “In addition, hepatocellular carcinomas exhibit a tumorinitiating population that can be identified by expression of another cell surface marker, epithelial cell adhesion molecule (EpCAM), which is expressed in normal epithelial progenitor cells (Yamashita et al., 2009).”