title: EpCAM, a potential therapeutic target for esophageal squamous cell carcinoma.
abstract: BACKGROUND
  Molecular-targeted drugs are not available for esophageal squamous cell carcinoma (ESCC), which has a poor prognosis. We investigated the clinicopathological significance of epithelial cell adhesion molecule (EpCAM) expression and the utility of EpCAM as a potential therapeutic target.
  
  
  METHODS
  The relationship between EpCAM expression and clinicopathological factors was examined by immunohistochemistry in 74 patients with resectable ESCC. A total of ten ESCC cell lines were analyzed for EpCAM expression. The effects of EpCAM knockdown in TE4, TE10, and TE14 cells were examined with regard to cell proliferation and gene expression in vitro and tumor growth in vivo. The antitumor effect of catumaxomab in ESCC cell lines was examined.
  
  
  RESULTS
  EpCAM overexpression was associated with poor survival in ESCC patients (P = 0.026). Multivariate Cox regression analysis showed that EpCAM overexpression was a significant and independent prognostic factor for surgically treated ESCC (P = 0.004). TE4 and TE10 cells showed high EpCAM expression, in contrast to TE14. EpCAM siRNA knockdown in TE4 and TE10 cells downregulated CCND1 and CCNE2 and suppressed cell proliferation. Low EpCAM expression reduced tumorigenesis; TE4 cells initiated tumorigenesis in seven of the ten mice injected, whereas shRNA knockdown resulted in smaller tumors in two of ten mice at 6 weeks after transplantation. Concentration- and time-dependent antitumor effects of catumaxomab were observed in TE4 and TE10 cells.
  
  
  CONCLUSIONS
  EpCAM overexpression is an independent prognostic factor for surgically treated ESCC. EpCAM contributes to cell proliferation and tumorigenesis and may be a useful therapeutic target for ESCC.
authors.affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Matsuda
authors.forename: Hiroya
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Sachiko
authors.initials: S
authors.lastname: Matsuda
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Hiraiwa
authors.forename: Taku
authors.initials: T
authors.lastname: Miyasho
authors.forename: Minoru
authors.initials: M
authors.lastname: Okamoto
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Kawasako
authors.forename: Rieko
authors.initials: R
authors.lastname: Nakamura
authors.forename: Tsunehiro
authors.initials: T
authors.lastname: Takahashi
authors.forename: Norihito
authors.initials: N
authors.lastname: Wada
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kawakubo
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saikawa
authors.forename: Tai
authors.initials: T
authors.lastname: Omori
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitagawa
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D000071858:Epithelial Cell Adhesion Molecule; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D018033:Antibodies, Bispecific; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C522419:catumaxomab