title: B7h triggering inhibits umbilical vascular endothelial cell adhesiveness to tumor cell lines and polymorphonuclear cells.
abstract: Vascular endothelial cells (ECs) are key players in leukocyte recruitment into tissues and metastatic dissemination of tumor cells. ECs express B7h, which is the ligand of the ICOS T cell costimulatory molecule. The aim of this work was to assess the effect of B7h triggering by a soluble form of ICOS (ICOS-Fc) on the adhesion of colon carcinoma cell lines to HUVECs. We found that B7h triggering inhibited HUVEC adhesiveness to HT29 and DLD1 cells (by 50 and 35%, respectively) but not to HCT116 cells. The effect was dependent on the ICOS-Fc dose and was detectable as early as 30 min after treatment and was still present after 24 h. It was inhibited by soluble anti-ICOS reagents (mAb and B7h-Fc) and silencing of B7h on HUVECs, and it was not displayed by an F119S mutated form of ICOS-Fc that does not bind B7h. HUVEC treatment with ICOS-Fc did not modulate expression of adhesion molecules and cytokines, but it substantially downmodulated ERK phosphorylation induced by E-selectin triggering or osteopontin, which may influence HUVEC adhesiveness. Moreover, HUVEC treatment with ICOS-Fc also inhibited adhesion of polymorphonuclear cells and several tumor cell lines from different origins. Therefore, the B7h-ICOS interaction may modulate spreading of cancer metastases and recruitment of polymorphonuclear cells in inflammatory sites, which opens a view on the use of ICOS-Fc as an immunomodulatory drug.
authors.affiliation: Department of Anatomy, Pharmacology and Experimental Medicine, University of Torino, Torino, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Dianzani
authors.forename: Rosalba
authors.initials: R
authors.lastname: Minelli
authors.forename: Riccardo
authors.initials: R
authors.lastname: Mesturini
authors.forename: Annalisa
authors.initials: A
authors.lastname: Chiocchetti
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Barrera
authors.forename: Sabrina
authors.initials: S
authors.lastname: Boscolo
authors.forename: Chiara
authors.initials: C
authors.lastname: Sarasso
authors.forename: Casimiro Luca
authors.initials: CL
authors.lastname: Gigliotti
authors.forename: Daniele
authors.initials: D
authors.lastname: Sblattero
authors.forename: Junji
authors.initials: J
authors.lastname: Yagi
authors.forename: Josè Maria
authors.initials: JM
authors.lastname: Rojo
authors.forename: Roberto
authors.initials: R
authors.lastname: Fantozzi
authors.forename: Umberto
authors.initials: U
authors.lastname: Dianzani
mesh_terms: D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D060890:B7-H1 Antigen; D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014470:Umbilical Cord / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D015815:Cell Adhesion Molecules; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein