Epithelial cell adhesion molecule fragments and signaling in primary human liver cells

Epithelial Cell Adhesion Molecule (EpCAM), or CD326, is a trans‐membrane glycoprotein expressed by multiple normal epithelia as well as carcinoma. Human hepatic stem cells and bile duct epithelium of the liver are EpCAM positive. In tumor cell lines, its intracellular domain can be released after cl...

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Bibliographic Details
Published in:Journal of cellular physiology 2018-06, Vol.233 (6), p.4841-4851
Main Authors: Gerlach, Jörg C., Foka, Hubert G., Thompson, Robert L., Gridelli, Bruno, Schmelzer, Eva
Format: Article
Language:English
Subjects:
ADAM17 Protein - genetics
ADAM17 Protein - metabolism
Adhesion
Adult Stem Cells - drug effects
Adult Stem Cells - metabolism
Bile ducts
CD326
Cell adhesion
Cell adhesion & migration
Cell adhesion molecules
Cell proliferation
Cell Proliferation - drug effects
Cleavage
Colorectal Neoplasms - genetics
Colorectal Neoplasms - metabolism
Colorectal Neoplasms - pathology
EpCAM
Epithelial Cell Adhesion Molecule - genetics
Epithelial Cell Adhesion Molecule - metabolism
Epithelial cells
Epithelium
Fetal Stem Cells - drug effects
Fetal Stem Cells - metabolism
Fetuses
Fragmentation
Fragments
Gene expression
Gene Expression Regulation
Glycoproteins
Glycosylation
hepatocyte
Hepatocytes
HT29 Cells
Humans
Hydroxamic Acids - pharmacology
Inhibitors
Intracellular
Intracellular signalling
Liver
Liver - cytology
Liver - drug effects
Liver - metabolism
Neoplastic Stem Cells - drug effects
Neoplastic Stem Cells - metabolism
Neoplastic Stem Cells - pathology
Nuclei
Nuclei (cytology)
Peptide Fragments - metabolism
Primary Cell Culture
progenitor
Protein Domains
Signal Transduction - drug effects
siRNA
stem cell
Stem cells
Tumor cell lines
Tumor cells
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Description
Summary:Epithelial Cell Adhesion Molecule (EpCAM), or CD326, is a trans‐membrane glycoprotein expressed by multiple normal epithelia as well as carcinoma. Human hepatic stem cells and bile duct epithelium of the liver are EpCAM positive. In tumor cell lines, its intracellular domain can be released after cleavage of the extracellular domain. Within the cell nucleus, it induces cell proliferation, but cleavage depends on cell contact. Fragments of various lengths have been described in tumor cells. Despite its described important role in proliferation in tumor cells, there is not much known about the expression and role of EpCAM fragments in primary human liver cells. Here, we demonstrate that EpCAM protein fragments and function are considerable different between tumor cells, normal fetal and adult liver cells. Contrary to previously reported findings in tumor cells, gene knockdown or treatment with an inhibitor of the cleavage enzyme ADAM17 (TACE) rather increased cell numbers in primary human fetal liver‐derived EpCAM‐positive cells. EpCAM fragment sizes were not affected by treatment with inhibitor. Knockdown of EPCAM gene expression by siRNA in sorted cells did not significantly affect proliferation‐associated genes or cell numbers. The intracellular domain could not be detected within cell nuclei of fetal and adult liver cells. In conclusion, signaling through the intracellular domain of EpCAM appears to be a mechanism that induces proliferation specifically in tumorigenic cells but not in normal primary EpCAM‐positive liver cells. Epithelial Cell Adhesion Molecule (EpCAM), or CD326, is a trans‐membrane glycoprotein expressed by multiple carcinoma as well as normal human hepatic stem cells and bile duct epithelium of the liver. Here, we demonstrate that EpCAM protein fragments and function are different between tumor cells, normal fetal, and adult liver cells. Signaling through the intracellular domain of EpCAM appears to be a mechanism that induces proliferation in tumorigenic cells but not in normal primary EpCAM‐positive liver cells.
ISSN:0021-9541
1097-4652
DOI:10.1002/jcp.26286