Hepatic stellate cells promote upregulation of epithelial cell adhesion molecule and epithelial-mesenchymal transition in hepatic cancer cells

Abstract EpCAM (epithelial cell adhesion molecule) was discovered four decades ago as a tumor antigen on colorectal carcinomas. Owing to its frequent and high expression on carcinomas and their metastases, EpCAM serves as a prognostic marker, a therapeutic target, and an anchor molecule on circulating and disseminated tumor cells (CTCs/DTCs), which are considered the major source for metastatic cancer cells. Today, EpCAM is reckoned as a multi-functional transmembrane protein involved in the regulation of cell adhesion, proliferation, migration, stemness, and epithelial-to-mesenchymal transition (EMT) of carcinoma cells. To fulfill these functions, EpCAM is instrumental in intra- and intercellular signaling as a full-length molecule and following regulated intramembrane proteolysis, generating functionally active extra- and intracellular fragments. Intact EpCAM and its proteolytic fragments interact with claudins, CD44, E-cadherin, epidermal growth factor receptor (EGFR), and intracellular signaling components of the WNT and Ras/Raf pathways, respectively. This plethora of functions contributes to shaping intratumor heterogeneity and partial EMT, which are major determinants of the clinical outcome of carcinoma patients. EpCAM represents a marker for the epithelial status of primary and systemic tumor cells and emerges as a measure for the metastatic capacity of CTCs. Consequentially, EpCAM has reclaimed potential as a prognostic marker and target on primary and systemic tumor cells.

Download Full-text

Epithelial Cell Adhesion Molecule: An Anchor to Isolate Clinically Relevant Circulating Tumor Cells

Cells ◽

10.3390/cells9081836 ◽

2020 ◽

Vol 9 (8) ◽

pp. 1836

Author(s):

Zahra Eslami-S ◽

Luis Enrique Cortés-Hernández ◽

Catherine Alix-Panabières

Keyword(s):

Cell Adhesion ◽

Epithelial Cell ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Adhesion Molecule ◽

Cell Adhesion Molecule ◽

Epithelial To Mesenchymal Transition ◽

Epithelial Cell Adhesion Molecule ◽

Mesenchymal Transition ◽

Advantages And Disadvantages

In the last few decades, the epithelial cell adhesion molecule (EpCAM) has received increased attention as the main membrane marker used in many enrichment technologies to isolate circulating tumor cells (CTCs). Although there has been a great deal of progress in the implementation of EpCAM-based CTC detection technologies in medical settings, several issues continue to limit their clinical utility. The biology of EpCAM and its role are not completely understood but evidence suggests that the expression of this epithelial cell-surface protein is crucial for metastasis-competent CTCs and may not be lost completely during the epithelial-to-mesenchymal transition. In this review, we summarize the most significant advantages and disadvantages of using EpCAM as a marker for CTC enrichment and its potential biological role in the metastatic cascade.

Download Full-text

Solubility assessment of single-chain antibody fragment against epithelial cell adhesion molecule extracellular domain in four Escherichia coli strains

Journal of Genetic Engineering and Biotechnology ◽

10.1186/s43141-021-00126-1 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Fatemeh Sadat Javadian ◽

Majid Basafa ◽

Aidin Behravan ◽

Atieh Hashemi

Keyword(s):

Escherichia Coli ◽

Cell Adhesion ◽

Epithelial Cell ◽

Adhesion Molecule ◽

Cell Adhesion Molecule ◽

Extracellular Domain ◽

Epithelial Cell Adhesion Molecule ◽

Single Chain ◽

E Coli ◽

The Impact

Abstract Background Overexpression of the EpCAM (epithelial cell adhesion molecule) in malignancies makes it an attractive target for passive immunotherapy in a wide range of carcinomas. In comparison with full-length antibodies, due to the small size, the scFvs (single-chain variable fragments) are more suitable for recombinant expression in E. coli (Escherichia coli). However, the proteins expressed in large amounts in E. coli tend to form inclusion bodies that need to be refolded which may result in poor recovery of bioactive proteins. Various engineered strains were shown to be able to alleviate the insolubility problem. Here, we studied the impact of four E. coli strains on the soluble level of anti-EpEX-scFv (anti-EpCAM extracellular domain-scFv) protein. Results Although results showed that the amount of soluble anti-EpEX-scFv obtained in BL21TM (DE3) (114.22 ± 3.47 mg/L) was significantly higher to those produced in the same condition in E. coli RosettaTM (DE3) (71.39 ± 0.31 mg/L), and OrigamiTM T7 (58.99 ± 0.44 mg/L) strains, it was not significantly different from that produced by E. coli SHuffleTM T7 (108.87 ± 2.71 mg/L). Furthermore, the highest volumetric productivity of protein reached 318.29 ± 26.38 mg/L in BL21TM (DE3). Conclusions Although BL21TM (DE3) can be a suitable strain for high-level production of anti-EpEX-scFv protein, due to higher solubility yield (about 55%), E. coli SHuffleTM T7 seems to be better candidate for soluble production of scfv compared to BL21TM (DE3) (solubility yield of about 30%).

Download Full-text