title: Soluble ICAM-1 secretion and its functional role as an autocrine growth factor in nasal NK/T cell lymphoma cells.
abstract: Nasal natural killer-T cell lymphoma (NNKTL) is associated with the Epstein-Barr virus and has distinct histologic features, such as angiocentric and polymorphous lymphoreticular infiltrates that contain too many cell types, including tumor and inflammatory cells. We have shown previously that intercellular adhesion molecule (ICAM)-1 is expressed in NNKTL cells, and that soluble ICAM-1 (sICAM-1) is significantly increased in patients' sera. However, the functional role of sICAM-1 remains unknown. In this study, we found that Epstein-Barr virus-positive NNKTL cell line SNK6 secreted sICAM-1 in a time-dependent manner. Moreover, exogenous sICAM-1 enhanced the growth of SNK6 cells in a dose-dependent manner. In comparison, neutralizing ICAM-1 and LFA-1 antibodies, as well as the LFA-1 blocker simvastatin, caused a dose-dependent reduction in the number of viable SNK6 cells. Double immunohistologic staining of NNKTL tissues confirmed that CD56 positive lymphoma cells coexpressed LFA-1. Moreover, serum sICAM-1 levels in NNKTL patients decreased after treatment, suggesting that the levels reflected disease progression. We conclude that NNKTL cells secrete sICAM-1 that acts as an autocrine factor for lymphoma progression, and suggest that simvastatin could be a potential candidate to treat NNKTL.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Asahikawa, Japan. miki@asahikawa-med.ac.jp
authors.forename: Miki
authors.initials: M
authors.lastname: Takahara
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nagato
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Komabayashi
authors.forename: Kazumi
authors.initials: K
authors.lastname: Yoshino
authors.forename: Seigo
authors.initials: S
authors.lastname: Ueda
authors.forename: Kan
authors.initials: K
authors.lastname: Kishibe
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Harabuchi
mesh_terms: D000328:Adult; D000368:Aged; D002455:Cell Division; D045744:Cell Line, Tumor; D005260:Female; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D016399:Lymphoma, T-Cell / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009669:Nose Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: D006133:Growth Substances; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1