Journal
JOURNAL OF GASTROENTEROLOGY
Volume 49, Issue 1, Pages 81-92Publisher
SPRINGER JAPAN KK
DOI: 10.1007/s00535-013-0773-6
Keywords
C-ERC/mesothelin; Colorectal cancer; Lymphatic invasion
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Funding
- Japan Society for the Promotion of Science (JSPS) through the Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program)
- Council for Science and Technology Policy (CSTP)
- Grants-in-Aid for Scientific Research [23590435, 221S0001] Funding Source: KAKEN
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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.
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