Human mesenchymal stem cells preferentially migrate toward highly oncogenic human hepatocellular carcinoma cells with activated EpCAM signaling

Endaya, Berwini; Guan, Sheng-Uei; Newman, Jennifer P.; Huynh, Hung; Sia, Kian Chuan; Chong, Siao Ting; Kok, Catherine Y. L.; Chung, Alexander Y. F.; Liu, Bin B.; Hui, Kam M.; Lam, Paula Yeng Po

doi:10.18632/oncotarget.17633

Cited by 14 publications

(13 citation statements)

References 33 publications

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“…These findings apply to other cancer tumor-initiating cells such as colorectal, ovarian, and hepatocellular carcinoma CSCs. [57][58][59][60] Also, CSCs EpCAM expression has been associated with therapy resistance and tumor bulk maintenance. 56,58,59,61 Importantly, EpCAM is one of the most reliable markers of circulating tumor cells (CTCs) in various carcinomas, and the presence of EpCAM + CTCs is related to poor outcome, like colorectal cancer, head and neck cancer, ovarian cancer, and breast cancer.…”

Section: Solid Cancermentioning

confidence: 99%

Cell-adhesion molecules and their soluble forms: Promising predictors of “tumor progression” and relapse in leukemia

et al. 2018

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Some surface markers are used to discriminate certain leukemic subpopulations that retain a greater oncogenic potential than others, and, for this reason, they were termed as leukemic stem cells, similar to the concept of cancer stem cells in carcinoma. Among these surface markers are proteins involved in cell-cell adhesion or cell-matrix adhesion, and they may play a role in the relapse of leukemia, similar to metastasis in carcinomas. The most important are epithelial cadherin, neural cadherin, epithelial cell-adhesion molecule, and CD44, which can be cleaved and released, and their soluble forms were found increased in serum levels of cancer patients, being implicated, in some cases, with progression, metastases, and relapse. In this review, we highlighted the role of these four adhesion molecules in carcinomas and hematological malignancies, mainly leukemia, and discuss if the serum levels of soluble forms can be correlated with the surface protein status on the leukemic cells. Accession of the soluble forms looks attractive, but their use as markers in cancer must be studied in association with other parameters, as there are significant changes in levels in other pathological conditions besides cancer. Studies correlating the levels of the forms with the status of the membrane-bound proteins in leukemic (stem) cells and correlating those parameters with relapse in leukemia may afford important knowledge and applicability of those serum markers in clinical practice. For instance, the expression of the membrane-bound forms of these adhesion proteins may have promising clinical use in leukemia and other hematological malignancies.

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Section: Solid Cancermentioning

confidence: 99%

Cell-adhesion molecules and their soluble forms: Promising predictors of “tumor progression” and relapse in leukemia

et al. 2018

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“…EPCAM (CD326) is an epithelial cell adhesion molecule that plays an important role in the self‐renewal and differentiation of embryonic stem cells. EPCAM‐positive liver cancer cells have self‐renewal and differentiation potential, and form highly invasive tumors in nude mice . In addition, activation of the Wnt‐ β ‐catenin signaling pathway leads to an increase in the number of EPCAM positive cells .…”

Section: Introductionmentioning

confidence: 99%

“…EPCAM-positive liver cancer cells have self-renewal and differentiation potential, and form highly invasive tumors in nude mice. 14 In addition, activation of the Wnt-β-catenin signaling pathway leads to an increase in the number of EPCAM positive cells. 15,16 CD90 + and CD44 + HCC cells demonstrated a more aggressive phenotype.…”

mentioning

confidence: 99%

Epithelial to mesenchymal transition is involved in ethanol promoted hepatocellular carcinoma cells metastasis and stemness

Chen

Wang

et al. 2018

Molecular Carcinogenesis

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Hepatocellular Carcinoma (HCC) is a malignant tumor with high rate of relapse and metastasis. Ethanol is a well‐known risk factor for HCC; it promotes the progression and aggressiveness of HCC. However, the underlying mechanism remains unclear. In clinic studies, we showed that alcohol consumption is positively correlated with TNM stage and vessel invasion; HCC patients with chronic drinking history had faster progression rate and poorer prognosis compared to non‐drinkers. In experimental models, ethanol exposure enhanced the metastasis, and invasion of HCC cells. Ethanol exposure increased cancer stem cells (CSC) population and enhanced stemness of HCC cells in vitro and in vivo. Mechanically, we found that ethanol exposure induced epithelial to mesenchymal transition (EMT) through activating Wnt/β‐catenin signaling pathway in HCC cells. We further demonstrated that β‐catenin siRNA or salinomycin (an inhibitor of Wnt/β‐catenin pathway) partially rescued ethanol‐induced EMT. In conclusion, this study suggested that ethanol exposure promotes the metastasis and stemness of HCC cells by inducing EMT.

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“…In contrast, down-regulation of EpCAM can inhibit the proliferation and invasion of tumor cells (39). EpCAM is a target gene of the wnt/β-catenin signaling pathway, which is considered a critical marker of tumor cells with the characteristics of stem cells (40). Besides, in vitro studies have also shown that EpCAM is a downstream target gene of transferrelated protein 1, and overexpression of transfer-related protein-1 can increase the expression of EpCAM, leading to enhanced invasion and metastasis of lung cancer (41).…”

Section: Discussionmentioning

confidence: 99%

Diagnostic rather than prognostic markers-relationship between EpCAM overexpression and lung cancer: a meta-analysis

Zhu¹,

Peng²,

Cheng³

et al. 2021

Ann Palliat Med

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Background: Epithelial cell adhesion molecule (EpCAM) is one of the most commonly used markers of cancer stem cells (CSCs). However, the diagnostic and prognostic significance of EpCAM in lung cancer remains largely undetermined. In the present study, we systematically summarized and elucidated the correlation between EpCAM overexpression and lung cancer through a meta-analysis.Methods: Six databases (PubMed, Web of Science, Cochrane Library, and Embase, CnKI and Wanfang Database) were systematically searched. Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) criteria were adopted to assess the qualities of the included studies. Relevant data were extracted for metaanalysis using the Stata12.0 software. Unadjusted mixed odds ratios (ORs) or hazard ratios (HRs) with 95% confidence interval (95% CI) were estimated to evaluate the correlation between EpCAM overexpression and lung cancer. The sensitivity and specificity of the included studies were used to construct the summary receiver operator characteristic (SROC) curve and calculate the area under the SROC curve (AUC).Results: A total of 14 studies consisting of 2,658 lung cancer patients were included following the PICOS principle. We found that the EpCAM expression was significantly higher in lung cancer patients compared with normal controls, including patients with benign pulmonary diseases (OR =63.71, 95% CI, 14.59-278.21, P=0.003) and healthy individuals (OR =520.08, 95% CI, 16.38-16,510.80, P=0.002), and its overexpression was negatively associated with the TNM stage (III + IV) (OR =0.41, 95% CI, 0.21-0.82, P=0.073. The combined sensitivity and specificity of EpCAM overexpression in the diagnosis of lung cancer were 0.79 (95% CI, 0.59-0.90) and 0.98 (95% CI, 0.95-0.99), respectively, and the SROC-AUC was 0.98 (95% CI, 0.97-0.99). Multivariate analysis of 322 lung cancer patients showed that there was no significant correlation between the EpCAM overexpression and prognosis of lung cancer (HR =2.28, 95% CI, 0.80-6.51, P=0.002). Deeks' funnel plot analysis showed the existence of publication bias (P=0.000).Conclusions: Our present findings suggested that EpCAM overexpression was not sensitive enough to predict the prognosis of lung cancer. Moreover, it was also a potential diagnostic indicator for lung cancer and correlated with TNM staging of lung cancer.

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Human mesenchymal stem cells preferentially migrate toward highly oncogenic human hepatocellular carcinoma cells with activated EpCAM signaling

Cited by 14 publications

References 33 publications

Cell-adhesion molecules and their soluble forms: Promising predictors of “tumor progression” and relapse in leukemia

Cell-adhesion molecules and their soluble forms: Promising predictors of “tumor progression” and relapse in leukemia

Epithelial to mesenchymal transition is involved in ethanol promoted hepatocellular carcinoma cells metastasis and stemness

Diagnostic rather than prognostic markers-relationship between EpCAM overexpression and lung cancer: a meta-analysis

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