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Updated: Jul 31, 2025
Patient-derived Orthotopic Xenograft Models for Human Urothelial Cell Carcinoma and Colorectal Cancer Tumor Growth and Spontaneous Metastasis
Published on: May 12, 2019
EpCAM tumor specificity and proteoform patterns in urothelial cancer
Franz F Dressler1,2, Sofie Hinrichs3, Marie C Roesch4
1Institute of Pathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany. franz-friedrich.dressler@charite.de.
Background:
The role of the epithelial cell adhesion molecule (EpCAM) in cancer is still unclear. EpCAM cleavage through regulated intramembrane proteolysis results in fragments which interact with both oncogenic and tumor suppressive pathways. Additionally, the EpCAM molecule itself is used as a descriptive therapeutic target in urothelial cancer (UC), while data on its actual tumor specificity remain limited.
Methods:
Samples from diagnostic formalin-fixed paraffin-embedded (FFPE) UC tissue and fresh-frozen UC cells were immunoblotted and used for qualitative characterization of five different EpCAM fragments. These expression patterns were quantified across a cohort of 76 samples with 52 UC and 24 normal urothelial samples. Cell viability effects of the extracellular EpEX fragment were assessed in the UC cell lines T24 and HT1376.
Results:
The proteolytic EpCAM fragments could be identified in clinical FFPE tissue specimens too. Neither overall nor fragment-specific EpCAM expression showed relevant tumor specificity. EpEX and its deglycosylated variant showed an inverse relationship across healthy and tumor tissue with a decrease of deglycosylated EpEX in tumors. However, extracellular EpEX did not show a relevant effect in vitro.
Conclusions:
EpCAM should not be regarded as tumor-specific in UC without patient-specific predictive testing. EpCAM fragment patterns indicate cancer-specific changes and could be involved in its complex tumor-biological role.
Insights
Epithelial cell adhesion molecule (EpCAM) fragments show cancer-specific changes in urothelial cancer (UC), but EpCAM itself is not tumor-specific. Further testing is needed for its use as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The role of Epithelial Cell Adhesion Molecule (EpCAM) in cancer remains unclear, with its fragments interacting in complex oncogenic and tumor-suppressive pathways.
- EpCAM is a therapeutic target in urothelial cancer (UC), but its tumor specificity is not well-established.
Purpose of the Study:
- To investigate the expression patterns of EpCAM fragments in urothelial cancer (UC) and assess their tumor specificity.
- To evaluate the in vitro effects of the EpCAM extracellular fragment (EpEX) on UC cell viability.
Main Methods:
- Immunoblotting of formalin-fixed paraffin-embedded (FFPE) UC tissue and fresh-frozen UC cells to characterize EpCAM fragments.
- Quantification of EpCAM fragment expression in 52 UC and 24 normal urothelial samples.
- In vitro assessment of EpEX fragment effects on T24 and HT1376 UC cell lines.
Main Results:
- Proteolytic EpCAM fragments were identified in clinical FFPE UC tissues.
- Neither overall nor fragment-specific EpCAM expression demonstrated significant tumor specificity.
- A decrease in deglycosylated EpEX was observed in tumors compared to healthy tissue, though EpEX showed no significant in vitro effect on cell viability.
Conclusions:
- EpCAM should not be considered tumor-specific in UC without predictive testing.
- EpCAM fragment patterns suggest cancer-specific alterations and may play a role in its complex tumor biology.
