TY - JOUR
T1 - B7h triggering inhibits the migration of tumor cell lines
AU - Dianzani, Chiara
AU - Minelli, Rosalba
AU - Gigliotti, Casimiro Luca
AU - Occhipinti, Sergio
AU - Giovarelli, Mirella
AU - Conti, Laura
AU - Boggio, Elena
AU - Shivakumar, Yogesh
AU - Baldanzi, Gianluca
AU - Malacarne, Valeria
AU - Orilieri, Elisabetta
AU - Cappellano, Giuseppe
AU - Fantozzi, Roberto
AU - Sblattero, Daniele
AU - Yagi, Junji
AU - Rojo, Josè Maria
AU - Chiocchetti, Annalisa
AU - Dianzani, Umberto
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2014/5/15
Y1 - 2014/5/15
N2 - Vascular endothelial cells (ECs) and several cancer cells express B7h, which is the ligand of the ICOS T cell costimulatory molecule. We have previously shown that B7h triggering via a soluble form of ICOS (ICOS-Fc) inhibits the adhesion of polymorphonuclear and tumor cell lines to HUVECs; thus, we suggested that ICOS-Fc may act as an anti-inflammatory and antitumor agent. Because cancer cell migration and angiogenesis are crucial for metastasis dissemination, the aim of this work was to evaluate the effect of ICOS-Fc on the migration of cancer cells and ECs. ICOS-Fc specifically inhibited the migration of HUVECs, human dermal lymphatic ECs, and the HT29, HCT116, PC-3, HepG2, JR8, and M14 tumor cell lines expressing high levels of B7h, whereas it was ineffective in the RPMI7932, PCF-2, LM, and BHT-101 cell lines expressing low levels of B7h. Furthermore, ICOS-Fc downmodulated hepatocyte growth factor facilitated the epithelial-to-mesenchymal transition in HepG2 cells. Moreover, ICOS-Fc downmodulated the phosphorylation of focal adhesion kinase and the expression of β-Pix in both HUVECs and tumor cell lines. Finally, treatment with ICOS-Fc inhibited the development of lung metastases upon injection of NOD-SCID-IL2Rγnull mice with CFPAC1 cells, as well as C57BL/6 mice with B16-F10 cells. Therefore, the B7h2ICOS interaction may modulate the spread of cancer metastases, which suggests the novel use of ICOS-Fc as an immunomodulatory drug. However, in the B16-F10-metastasized lungs, ICOS-Fc also increased IL-17A/RORc and decreased IL-10/Foxp3 expression, which indicates that it also exerts positive effects on the antitumor immune response.
AB - Vascular endothelial cells (ECs) and several cancer cells express B7h, which is the ligand of the ICOS T cell costimulatory molecule. We have previously shown that B7h triggering via a soluble form of ICOS (ICOS-Fc) inhibits the adhesion of polymorphonuclear and tumor cell lines to HUVECs; thus, we suggested that ICOS-Fc may act as an anti-inflammatory and antitumor agent. Because cancer cell migration and angiogenesis are crucial for metastasis dissemination, the aim of this work was to evaluate the effect of ICOS-Fc on the migration of cancer cells and ECs. ICOS-Fc specifically inhibited the migration of HUVECs, human dermal lymphatic ECs, and the HT29, HCT116, PC-3, HepG2, JR8, and M14 tumor cell lines expressing high levels of B7h, whereas it was ineffective in the RPMI7932, PCF-2, LM, and BHT-101 cell lines expressing low levels of B7h. Furthermore, ICOS-Fc downmodulated hepatocyte growth factor facilitated the epithelial-to-mesenchymal transition in HepG2 cells. Moreover, ICOS-Fc downmodulated the phosphorylation of focal adhesion kinase and the expression of β-Pix in both HUVECs and tumor cell lines. Finally, treatment with ICOS-Fc inhibited the development of lung metastases upon injection of NOD-SCID-IL2Rγnull mice with CFPAC1 cells, as well as C57BL/6 mice with B16-F10 cells. Therefore, the B7h2ICOS interaction may modulate the spread of cancer metastases, which suggests the novel use of ICOS-Fc as an immunomodulatory drug. However, in the B16-F10-metastasized lungs, ICOS-Fc also increased IL-17A/RORc and decreased IL-10/Foxp3 expression, which indicates that it also exerts positive effects on the antitumor immune response.
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U2 - 10.4049/jimmunol.1300587
DO - 10.4049/jimmunol.1300587
M3 - Article
C2 - 24729612
AN - SCOPUS:84901251138
SN - 0022-1767
VL - 192
SP - 4921
EP - 4931
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -