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Trefoil factor-3 expression in human colon cancer liver metastasis

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Abstract

Deaths from colorectal cancer are often due to liver metastasis. Trefoil factor-3 (TFF3) is expressed by normal intestinal epithelial cells and its expression is maintained throughout the colon adenoma-carcinoma sequence. Our previous work demonstrated a correlation between TFF3 expression and metastatic potential in an animal model of colon cancer. The aim of this study was to determine whether TFF3 is expressed in human colon cancer liver metastasis (CCLM) and whether inhibiting TFF3 expression in colon cancer cells would alter their invasive potential in vitro. Human CCLMs were analyzed at the mRNA and protein level for TFF3 expression. Two highly metastatic rat colon cancer cell lines that either natively express TFF3 (LN cells) or were transfected with TFF3 (LPCRI-2 cells), were treated with two rat TFF3 siRNA constructs (si78 and si365), and analyzed in an in vitro invasion assay. At the mRNA and protein level, TFF3 was expressed in 17/17 (100%) CCLMs and 10/11 (91%) primary colon cancers, but not in normal liver tissue. By real time PCR, TFF3 expression was markedly inhibited by both siRNA constructs in LN and LPCRI-2 cells. The si365 and si78 constructs inhibited invasion by 44% and 53%, respectively, in LN cells, and by 74% and 50%, respectively, in LPCRI-2 cells. These results provide further evidence that TFF3 contributes to the malignant behavior of colon cancer cells. These observations may have relevance for designing new diagnostic and treatment approaches to colorectal cancer.

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Acknowledgements

The authors wish to thank Ping Jiang for assistance with transfection experiments. Financial support: Supported in part by RO1-CA109189 and The Chemotherapy Foundation (SHI), the Lucille Markey Trust (MWB), The Peptic Ulcer and Gastric Cancer Foundation (JLW, SHI), and The Doris Duke Clinical Research Foundation (CT).

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Authors and Affiliations

  1. The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, The Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1069, New York, NY, 10029-6574, USA

    Mark Babyatsky, Xianyang Yio, Anli Chen, Jie-yu Zhang, Yan Zheng, Christina Twyman, Xiuliang Bao, J. Lawrence Werther & Steven Itzkowitz

  2. Department of Pediatrics, The Mount Sinai School of Medicine, New York, NY, 10029, USA

    Jing Lin

  3. Division of Surgical Oncology, Department of Surgery, The Mount Sinai School of Medicine, New York, NY, 10029, USA

    Myron Schwartz

  4. Department of Pathology, The Mount Sinai School of Medicine, New York, NY, 10029, USA

    Swan Thung

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  1. Mark Babyatsky
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Babyatsky, M., Lin, J., Yio, X. et al. Trefoil factor-3 expression in human colon cancer liver metastasis. Clin Exp Metastasis 26, 143–151 (2009). https://doi.org/10.1007/s10585-008-9224-9

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