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C-ERC/mesothelin provokes lymphatic invasion of colorectal adenocarcinoma

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Title: C-ERC/mesothelin provokes lymphatic invasion of colorectal adenocarcinoma
Authors: Kawamata, Futoshi Browse this author
Homma, Shigenori Browse this author
Kamachi, Hirofumi Browse this author →KAKEN DB
Einama, Takahiro Browse this author
Kato, Yasutaka Browse this author
Tsuda, Masumi Browse this author →KAKEN DB
Tanaka, Shinya Browse this author →KAKEN DB
Maeda, Masahiro Browse this author
Kajino, Kazunori Browse this author
Hino, Okio Browse this author
Takahashi, Norihiko Browse this author
Kamiyama, Toshiya Browse this author →KAKEN DB
Nishihara, Hiroshi Browse this author →KAKEN DB
Taketomi, Akinobu Browse this author →KAKEN DB
Todo, Satoru Browse this author →KAKEN DB
Keywords: C-ERC/mesothelin
Colorectal cancer
Lymphatic invasion
Issue Date: Jan-2014
Publisher: Springer Japan
Journal Title: Journal of gastroenterology
Volume: 49
Issue: 1
Start Page: 81
End Page: 92
Publisher DOI: 10.1007/s00535-013-0773-6
PMID: 23512344
Abstract: Background Lymph node metastasis is a key event of colorectal cancer (CRC) progression. Mesothelin is expressed in various types of malignant tumor and associated with an unfavorable prognosis. The full-length mesothelin (Full-ERC) is cleaved by protease into membrane-bound C-ERC/mesothelin and N-ERC/mesothelin which is secreted into the blood. The aim of this study was to examine the biological role of mesothelin in CRC by clinicopathological analysis and in vitro lymphatic invasion assay. Methods Ninety-one cases of CRC specimens were immunohistochemically examined and the localization of mesothelin in luminal membrane and/or cytoplasm was also evaluated. Lymphatic invasion assay was also performed using the human CRC cell line, WiDr, which was transfected with Full-, N- and C-ERC/mesothelin expression plasmids (Full-WiDr, N-WiDr and C-WiDr). Results Immunohistochemically, "luminal membrane positive" of mesothelin was identified in 37.4 %, and correlated with lymphatic permeation and lymph node metastasis, but not with patients' prognosis. Interestingly, among the patients with lymph node metastasis (N = 38), "luminal membrane positive" of mesothelin significantly correlated with unfavorable patients' outcome. In addition, lymphatic invasion assay revealed that Full-WiDr and C-WiDr more significantly invaded human lymphatic endothelial cells than the Mock-WiDr (P < 0.01). Conclusion The luminal membrane expression of mesothelin was associated with unfavorable prognosis of CRC patients with lymph nodemetastasis. Moreover, this is the first report to prove the biological function of C-ERC/mesothelin associated with lymphatic invasion of cancer in vitro.
Rights: The final publication is available at
Type: article (author version)
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 西原 広史

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