Bedeutung der therapeutischen Zielstruktur EpCAM (CD326) für die Progression von Ösophaguskarzinomen

Abstract

Introduction. EpCAM is an epithelial homophilic cell adhesion molecule that is de novo expressed in esophageal cancer. It is considered as one of the best-characterised tumour-related antigens and is an important target for molecular cancer therapies. However, the function of EpCAM in tumour progression is still poorly understood. Because esophageal cancer (ECA) is highly metastatic, we have tested in cell-based experiments whether EpCAM contributes to this aggressive phenotype. Material and Methods. We used a cohort of 7 human ECA cell lines (4 squamous cell carcinoma and 3 adenocarcinoma cell lines) that express EpCAM at different levels and which served us as a model system. To measure the potential effects of the loss of EpCAM expression, we used a lentiviral pGIPZ shRNAmir system with two different sh-RNAs directed against EpCAM and one control shRNA vector. The EpCAM-suppression of the transduced cells was tested by quantitative RT-PCR and Western blot. Cell lines with an 80 % reduction of EpCAM expression were further analysed. We used the »Fence-assay« to investigate the migration. The tumour cell invasion was assessed with a commercially available Matrigel-coated Transwell system. Results. The migration of EpCAMshRNA- transduced squamous cell carcinoma cells was reduced by 30–50 % compared to tumour cells transduced with the control vector. A 3–4 % reduction of the invasion was observed. Both, the reduction in migration and invasion was statistically significant. Conclusion. Our data indicate a relevance of EpCAM in the progression of ECA. In view of the absence of effective systemic therapies for ECA, EpCAM appears to be an extremely attractive therapeutic target for adjuvant therapies. Therefore, our cell-based findings of EpCAM function are also of clinical relevance.