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: Tatsuo Matsuda, Hiroya Takeuchi, Sachiko Matsuda, Kunihiko Hiraiwa, Taku Miyasho, Minoru Okamoto, Kazufumi Kawasako, Rieko Nakamura, Tsunehiro Takahashi, Norihito Wada, Hirofumi Kawakubo, Yoshiro Saikawa, Tai Omori, Yuko Kitagawa
• Journal: Annals of surgical oncology (Ann Surg Oncol) Vol. 21 Suppl 3 Pg. S356-64 (Jun 2014) ISSN: 1534-4681 [Electronic] United States
• PMID: 24566863 (Publication Type: Journal Article)

Chemical References

• Antibodies, Bispecific
• Antigens, Neoplasm
• Biomarkers, Tumor
• Cell Adhesion Molecules
• EPCAM protein, human
• Epithelial Cell Adhesion Molecule
• RNA, Messenger
• RNA, Small Interfering
• catumaxomab

Topics

• Animals
• Antibodies, Bispecific (pharmacology)
• Antigens, Neoplasm (genetics, metabolism)
• Apoptosis
• Biomarkers, Tumor (genetics, metabolism)
• Blotting, Western
• Carcinoma, Squamous Cell (drug therapy, metabolism, mortality)
• Cell Adhesion Molecules (antagonists & inhibitors, genetics, metabolism)
• Cell Proliferation
• Epithelial Cell Adhesion Molecule
• Esophageal Neoplasms (drug therapy, metabolism, mortality)
• Female
• Flow Cytometry
• Follow-Up Studies
• Gene Expression Profiling
• Humans
• Immunoenzyme Techniques
• Lymphatic Metastasis
• Male
• Mice
• Mice, Nude
• Middle Aged
• Neoplasm Invasiveness
• Neoplasm Staging
• Oligonucleotide Array Sequence Analysis
• Prognosis
• RNA, Messenger (genetics)
• RNA, Small Interfering (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Survival Rate
• Tumor Cells, Cultured