title: C-ERC/mesothelin provokes lymphatic invasion of colorectal adenocarcinoma.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of General Surgery, Hokkaido University, Graduate School of Medicine, Sapporo, Japan.
authors.forename: Futoshi
authors.initials: F
authors.lastname: Kawamata
authors.forename: Shigenori
authors.initials: S
authors.lastname: Homma
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kamachi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Einama
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Kato
authors.forename: Masumi
authors.initials: M
authors.lastname: Tsuda
authors.forename: Shinya
authors.initials: S
authors.lastname: Tanaka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Maeda
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kajino
authors.forename: Okio
authors.initials: O
authors.lastname: Hino
authors.forename: Norihiko
authors.initials: N
authors.lastname: Takahashi
authors.forename: Toshiya
authors.initials: T
authors.lastname: Kamiyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishihara
authors.forename: Akinobu
authors.initials: A
authors.lastname: Taketomi
authors.forename: Satoru
authors.initials: S
authors.lastname: Todo
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000556:secondary* / Q000601:surgery; D014408:Biomarkers, Tumor / Q000378:metabolism / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D004729:Endothelium, Lymphatic / Q000473:pathology; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D000090204:Mesothelin; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism / Q000502:physiology; D011379:Prognosis; D012189:Retrospective Studies; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D009363:Neoplasm Proteins; D000090204:Mesothelin