title: EpCAM is overexpressed in local and metastatic prostate cancer, suppressed by chemotherapy and modulated by MET-associated miRNA-200c/205.
abstract: BACKGROUND
  Expression of epithelial cell adhesion molecule (EpCAM) is deregulated in epithelial malignancies. Beside its role in cell adhesion, EpCAM acts as signalling molecule with tumour-promoting functions. Thus, EpCAM is part of the molecular network of oncogenic receptors and considered an interesting therapeutic target.
  
  
  METHODS
  Here, we thoroughly characterised EpCAM expression on mRNA and protein level in comprehensive tissue studies including non-cancerous prostate specimens, primary tumours of different grades and stages, metastatic lesions, and therapy-treated tumour specimens, as well as in prostate cancer cell lines.
  
  
  RESULTS
  Epithelial cell adhesion molecule was overexpressed at mRNA and at protein level in prostate cancer tissues and cell lines. Altered EpCAM expression was an early event in prostate carcinogenesis with an upregulation in low-grade cancers and further induction in high-grade tumours and metastatic lesions. Interestingly, EpCAM was repressed upon induction of epithelial-to-mesenchymal transition (EMT) following chemotherapeutic treatment with docetaxel. Oppositely, re-induction of the epithelial phenotype through miRNAs miR-200c and miR-205, two inducers of mesenchymal-to-epithelial transition (MET), led to re-induction of EpCAM in chemoresistant cells. Furthermore, we prove that EpCAM cleavage, the first step of EpCAM signalling takes place in prostate cancer cells but in contrast to other cancer entities, EpCAM has no measurable impact on the proliferative behaviour of prostate cells, in vitro.
  
  
  CONCLUSIONS
  In conclusion, our data confirm that EpCAM overexpression is an early event during prostate cancer progression. Epithelial cell adhesion molecule displays a dynamic, heterogeneous expression and associates with epithelial cells rather than mesenchymal, chemoresistant cells along with processes of EMT and MET.
authors.affiliation: 1] Experimental Urology, Department of Urology, Innsbruck Medical University, Innsbruck, Austria [2] Department of Otorhinolaryngology, Head and Neck Surgery, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Massoner
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Thomm
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Mack
authors.affiliation: Laboratory of Experimental Oncology, Tyrolean Cancer Research Institute, Innsbruck, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Untergasser
authors.affiliation: Laboratory of Experimental Oncology, Tyrolean Cancer Research Institute, Innsbruck, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Martowicz
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Bobowski
authors.affiliation: Experimental Urology, Department of Urology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Klocker
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Gires
authors.affiliation: Experimental Urology, Department of Urology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Puhr
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D000071858:Epithelial Cell Adhesion Molecule; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000187:drug effects / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D043823:Taxoids / Q000494:pharmacology
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D035683:MicroRNAs; D012333:RNA, Messenger; D043823:Taxoids; D000077143:Docetaxel