Overexpression of epithelial cell adhesion molecule as a predictor of poor outcome in patients with hepatocellular carcinoma

Ko, Chih‐Jan; Li, Chia‐Jung; Wu, Meng‐Yu; Chu, Pei‐Yi

doi:10.3892/etm.2018.6794

Cited by 12 publications

(10 citation statements)

References 39 publications

(40 reference statements)

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“…Kaplan–Meier analyses showed that at advanced clinical stages, high EpCAM expression and poor differentiation grade were associated with poor survival rates. These results collectively support the utility of EpCAM in HCC as a predictive biomarker for unfavorable prognosis [ 73 ].…”

Section: Identification and Plasticity Of Lcscssupporting

confidence: 75%

Cancer Stem Cell Functions in Hepatocellular Carcinoma and Comprehensive Therapeutic Strategies

Liu

Yeh

Lin

2020

Cells

175

134

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Hepatocellular carcinoma (HCC) is a significant cause of cancer-related mortality owing to resistance to traditional treatments and tumor recurrence after therapy, which leads to poor therapeutic outcomes. Cancer stem cells (CSC) are a small subset of tumor cells with the capability to influence self-renewal, differentiation, and tumorigenesis. A number of surface markers for liver cancer stem cell (LCSC) subpopulations (EpCAM, CD133, CD44, CD13, CD90, OV-6, CD47, and side populations) in HCC have been identified. LCSCs play critical roles in regulating HCC stemness, self-renewal, tumorigenicity, metastasis, recurrence, and therapeutic resistance via genetic mutations, epigenetic disruption, signaling pathway dysregulation, or alterations microenvironment. Accumulating studies have shown that biomarkers for LCSCs contribute to diagnosis and prognosis prediction of HCC, supporting their utility in clinical management and development of therapeutic strategies. Preclinical and clinical analyses of therapeutic approaches for HCC using small molecule inhibitors, oncolytic measles viruses, and anti-surface marker antibodies have demonstrated selective, efficient, and safe targeting of LCSC populations. The current review focuses on recent reports on the influence of LCSCs on HCC stemness, tumorigenesis, and multiple drug resistance (MDR), along with LCSC-targeted therapeutic strategies for HCC.

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Section: Identification and Plasticity Of Lcscssupporting

confidence: 75%

Cancer Stem Cell Functions in Hepatocellular Carcinoma and Comprehensive Therapeutic Strategies

Liu

Yeh

Lin

2020

Cells

175

134

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“…In HCC, the loss of HNF4 [9,51,56] and expression of the cancer stem cell (CSC) markers CD44, CK19, Sox9, and EpCAM are considered to be indicators for poor prognosis [57,58,59,60]. In N-HCC25, these CSC markers were expressed in all passages.…”

Section: Discussionmentioning

confidence: 99%

A Newly Established Murine Cell Line as a Model for Hepatocellular Cancer in Non-Alcoholic Steatohepatitis

Kroh

Walter

Schüler

et al. 2019

IJMS

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Non-alcoholic steatohepatitis (NASH) has become a major risk factor for hepatocellular cancer (HCC) due to the worldwide increasing prevalence of obesity. However, the pathophysiology of NASH and its progression to HCC is incompletely understood. Thus, the aim of this study was to generate a model specific NASH-derived HCC cell line. A murine NASH-HCC model was conducted and the obtained cancer cells (N-HCC25) were investigated towards chromosomal aberrations, the expression of cell type-specific markers, dependency on nutrients, and functional importance of mTOR. N-HCC25 exhibited several chromosomal aberrations as compared to healthy hepatocytes. Hepatocytic (HNF4), EMT (Twist, Snail), and cancer stem cell markers (CD44, EpCAM, CK19, Sox9) were simultaneously expressed in these cells. Proliferation highly depended on the supply of glucose and FBS, but not glutamine. Treatment with a second generation mTOR inhibitor (KU-0063794) resulted in a strong decrease of cell growth in a dose-dependent manner. In contrast, a first generation mTOR inhibitor (Everolimus) only slightly reduced cell proliferation. Cell cycle analyses revealed that the observed growth reduction was most likely due to G1/G0 cell cycle arrest. These results indicate that N-HCC25 is a highly proliferative HCC cell line from a NASH background, which might serve as a suitable in vitro model for future investigations of NASH-derived HCC.

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“…These data suggest that EpCAM could be a potential target for the diagnosis and therapy of hepatic cancers. Yamashita et al demonstrated that activation of the Wnt/β-catenin signaling pathway stimulates EpCAM expression which, in turn, negatively affects the prognosis of HCC patients [ 103 , 104 ]. Wang et al [ 105 ] and Arzumanyan et al [ 106 ] demonstrated that hepatitis B antigen HBx promotes the self-renewal and tumorigenicity of EpCAM + hepatic progenitor cells by stimulating β-catenin signaling and miR-181 expression.…”

Section: Surface Marker-based Therapiesmentioning

confidence: 99%

Targeting Liver Cancer Stem Cells: An Alternative Therapeutic Approach for Liver Cancer

Lee

Hong

2020

Cancers

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The first report of cancer stem cell (CSC) from Bruce et al. has demonstrated the relatively rare population of stem-like cells in acute myeloid leukemia (AML). The discovery of leukemic CSCs prompted further identification of CSCs in multiple types of solid tumor. Recently, extensive research has attempted to identity CSCs in multiple types of solid tumors in the brain, colon, head and neck, liver, and lung. Based on these studies, we hypothesize that the initiation and progression of most malignant tumors rely largely on the CSC population. Recent studies indicated that stem cell-related markers or signaling pathways, such as aldehyde dehydrogenase (ALDH), CD133, epithelial cell adhesion molecule (EpCAM), Wnt/β-catenin signaling, and Notch signaling, contribute to the initiation and progression of various liver cancer types. Importantly, CSCs are markedly resistant to conventional therapeutic approaches and current targeted therapeutics. Therefore, it is believed that selectively targeting specific markers and/or signaling pathways of hepatic CSCs is an effective therapeutic strategy for treating chemotherapy-resistant liver cancer. Here, we provide an overview of the current knowledge on the hepatic CSC hypothesis and discuss the specific surface markers and critical signaling pathways involved in the development and maintenance of hepatic CSC subpopulations.

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Overexpression of epithelial cell adhesion molecule as a predictor of poor outcome in patients with hepatocellular carcinoma

Cited by 12 publications

References 39 publications

Cancer Stem Cell Functions in Hepatocellular Carcinoma and Comprehensive Therapeutic Strategies

Cancer Stem Cell Functions in Hepatocellular Carcinoma and Comprehensive Therapeutic Strategies

A Newly Established Murine Cell Line as a Model for Hepatocellular Cancer in Non-Alcoholic Steatohepatitis

Targeting Liver Cancer Stem Cells: An Alternative Therapeutic Approach for Liver Cancer

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