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.

B7h Triggering Inhibits Umbilical Vascular Endothelial Cell Adhesiveness to Colon Carcinoma Cell Lines and Polymorphonuclear Cells. / Minelli R; Mesturini R; Chiocchetti A; Barrera G; Dianzani C; Dianzani U. - In: THE AMERICAN JOURNAL OF PATHOLOGY. - ISSN 0002-9440. - 177(2010), pp. IM 08--. ((Intervento presentato al convegno XXX National Congress of Società Italiana di Patologia, 2010 October 14-17, Salerno, Italy tenutosi a Salerno nel 2010 October 14-17,.

B7h Triggering Inhibits Umbilical Vascular Endothelial Cell Adhesiveness to Colon Carcinoma Cell Lines and Polymorphonuclear Cells.

MINELLI, ROSALBA;BARRERA, Giuseppina;DIANZANI, Chiara;
2010

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.
XXX National Congress of Società Italiana di Patologia, 2010 October 14-17, Salerno, Italy
Salerno
2010 October 14-17,
177
IM 08
-
Minelli R; Mesturini R; Chiocchetti A; Barrera G; Dianzani C; Dianzani U
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1514559
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