B7h triggering inhibits umbilical vascular endothelial cell adhesiveness to tumor cell lines and polymorphonuclear cells.
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.
Dianzani
Chiara
C
Department of Anatomy, Pharmacology and Experimental Medicine, University of Torino, Torino, Italy.
Minelli
Rosalba
R
Mesturini
Riccardo
R
Chiocchetti
Annalisa
A
Barrera
Giuseppina
G
Boscolo
Sabrina
S
Sarasso
Chiara
C
Gigliotti
Casimiro Luca
CL
Sblattero
Daniele
D
Yagi
Junji
J
Rojo
Josè Maria
JM
Fantozzi
Roberto
R
Dianzani
Umberto
U
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
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