C-ERC/mesothelin provokes lymphatic invasion of colorectal adenocarcinoma

Futoshi Kawamata, Shigenori Homma, Hirofumi Kamachi, Takahiro Einama, Yasutaka Kato, Masumi Tsuda, Shinya Tanaka, Masahiro Maeda, Kazunori Kajino, Okio Hino, Norihiko Takahashi, Toshiya Kamiyama, Hiroshi Nishihara, Akinobu Taketomi, Satoru Todo

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 node metastasis. Moreover, this is the first report to prove the biological function of C-ERC/mesothelin associated with lymphatic invasion of cancer in vitro.

Original languageEnglish
Pages (from-to)81-92
Number of pages12
JournalJournal of gastroenterology
Volume49
Issue number1
DOIs
Publication statusPublished - 2014 Jan 1
Externally publishedYes

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Adenocarcinoma
Colorectal Neoplasms
Lymph Nodes
Membranes
Neoplasm Metastasis
mesothelin
Neoplasms
Cytoplasm
Plasmids
Peptide Hydrolases
Endothelial Cells
Cell Line

Keywords

  • C-ERC/mesothelin
  • Colorectal cancer
  • Lymphatic invasion

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Kawamata, F., Homma, S., Kamachi, H., Einama, T., Kato, Y., Tsuda, M., ... Todo, S. (2014). C-ERC/mesothelin provokes lymphatic invasion of colorectal adenocarcinoma. Journal of gastroenterology, 49(1), 81-92. https://doi.org/10.1007/s00535-013-0773-6

C-ERC/mesothelin provokes lymphatic invasion of colorectal adenocarcinoma. / Kawamata, Futoshi; Homma, Shigenori; Kamachi, Hirofumi; Einama, Takahiro; Kato, Yasutaka; Tsuda, Masumi; Tanaka, Shinya; Maeda, Masahiro; Kajino, Kazunori; Hino, Okio; Takahashi, Norihiko; Kamiyama, Toshiya; Nishihara, Hiroshi; Taketomi, Akinobu; Todo, Satoru.

In: Journal of gastroenterology, Vol. 49, No. 1, 01.01.2014, p. 81-92.

Research output: Contribution to journalArticle

Kawamata, F, Homma, S, Kamachi, H, Einama, T, Kato, Y, Tsuda, M, Tanaka, S, Maeda, M, Kajino, K, Hino, O, Takahashi, N, Kamiyama, T, Nishihara, H, Taketomi, A & Todo, S 2014, 'C-ERC/mesothelin provokes lymphatic invasion of colorectal adenocarcinoma', Journal of gastroenterology, vol. 49, no. 1, pp. 81-92. https://doi.org/10.1007/s00535-013-0773-6
Kawamata, Futoshi ; Homma, Shigenori ; Kamachi, Hirofumi ; Einama, Takahiro ; Kato, Yasutaka ; Tsuda, Masumi ; Tanaka, Shinya ; Maeda, Masahiro ; Kajino, Kazunori ; Hino, Okio ; Takahashi, Norihiko ; Kamiyama, Toshiya ; Nishihara, Hiroshi ; Taketomi, Akinobu ; Todo, Satoru. / C-ERC/mesothelin provokes lymphatic invasion of colorectal adenocarcinoma. In: Journal of gastroenterology. 2014 ; Vol. 49, No. 1. pp. 81-92.
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T1 - C-ERC/mesothelin provokes lymphatic invasion of colorectal adenocarcinoma

AU - Kawamata, Futoshi

AU - Homma, Shigenori

AU - Kamachi, Hirofumi

AU - Einama, Takahiro

AU - Kato, Yasutaka

AU - Tsuda, Masumi

AU - Tanaka, Shinya

AU - Maeda, Masahiro

AU - Kajino, Kazunori

AU - Hino, Okio

AU - Takahashi, Norihiko

AU - Kamiyama, Toshiya

AU - Nishihara, Hiroshi

AU - Taketomi, Akinobu

AU - Todo, Satoru

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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 node metastasis. Moreover, this is the first report to prove the biological function of C-ERC/mesothelin associated with lymphatic invasion of cancer in vitro.

AB - 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 node metastasis. Moreover, this is the first report to prove the biological function of C-ERC/mesothelin associated with lymphatic invasion of cancer in vitro.

KW - C-ERC/mesothelin

KW - Colorectal cancer

KW - Lymphatic invasion

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