Year-end Sale % OFF 
Abstract
BackgroundWe previously demonstrated that nuclear and cytoplasmic accumulation of the intracellular domain (Ep-ICD) of epithelial cell adhesion molecule (EpCAM) accompanied by a reciprocal reduction of its extracellular domain (EpEx), occurs in aggressive thyroid cancers. This study was designed to determine whether similar accumulation of Ep-ICD is a common event in other epithelial cancers.Methodology and ResultsTen epithelial cancers were immunohistochemically analyzed using Ep-ICD and EpEx domain-specific antibodies. The subcellular localization of EpEx and Ep-ICD in the human colon adenocarcinoma cell line CX-1 was observed using immunofluorescence. Nuclear and cytoplasmic Ep-ICD expression was increased in cancers of the breast (31 of 38 tissues, 82%), prostate (40 of 49 tissues, 82%), head and neck (37 of 57 tissues, 65%) and esophagus (17 of 46 tissues, 37%) compared to their corresponding normal tissues that showed membrane localization of the protein. Importantly, Ep-ICD was not detected in the nuclei of epithelial cells in most normal tissues. High nuclear and cytoplasmic Ep-ICD accumulation also occurred in the other six epithelial cancer types analyzed - lung, colon, liver, bladder, pancreatic, and ovarian. A concomitant reduction in membrane EpEx expression was observed in a subset of all cancer types. Receiver operating characteristic curve analysis revealed nuclear Ep-ICD distinguished breast cancers with 82% sensitivity and 100% specificity and prostate cancers with 82% sensitivity and 78% specificity. Similar findings were observed for cytoplasmic accumulation of Ep-ICD in these cancers. We provide clinical evidence of increased nuclear and cytoplasmic Ep-ICD accumulation and a reduction in membranous EpEx in these cancers.ConclusionsIncreased nuclear and cytoplasmic Ep-ICD was observed in all epithelial cancers analyzed and distinguished them from normal tissues with high-sensitivity, specificity, and AUC. Development of a robust high throughput assay for Ep-ICD will facilitate the determination of its diagnostic, prognostic and therapeutic relevance in epithelial cancers.
Highlights
Epithelial cell adhesion molecule (EpCAM) is a 40 kDa transmembrane glycoprotein that serves important roles in cell adhesion, cell proliferation, differentiation, migration, cell cycle regulation and is implicated in cancer and stem cell signalling [1]
Increased nuclear and cytoplasmic Ep-ICD was observed in all epithelial cancers analyzed and distinguished them from normal tissues with high-sensitivity, specificity, and area under the curve (AUC)
We reported nuclear and cytoplasmic accumulation of Ep-ICD in different subtypes of thyroid cancers that was associated with a reciprocal reduction in membranous Ep-CAM external domain (EpEx), and observed a correlation of nuclear Ep-ICD accumulation with tumor aggressiveness and poor disease prognosis [28]
Summary
Epithelial cell adhesion molecule (EpCAM) is a 40 kDa transmembrane glycoprotein that serves important roles in cell adhesion, cell proliferation, differentiation, migration, cell cycle regulation and is implicated in cancer and stem cell signalling [1]. EpCAM is one of the most widely investigated proteins in human cancers, frequently overexpressed in human malignancies, localized on the plasma membrane of tumor cells and albeit at lower levels in the normal epithelia [2,3,4,5,6,7,8,9,10,11,12,13,14,15, 16,17] All these studies used antibodies directed against the extracellular domain of EpCAM (EpEx) [13]. Most clinical trials using murine monoclonal antibodies namely, edrecolomab in colorectal cancer, or the humanized antibody, adecatumumab, in breast cancer have shown limited efficacy [14,22] An understanding of these limitations poses a challenge for oncologists and is of great importance for future development of more effective anti-EpCAM strategies. This study was designed to determine whether similar accumulation of Ep-ICD is a common event in other epithelial cancers
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
