1. B7h triggering inhibits the migration of tumor cell lines
- Author
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Dianzani, Chiara, Minelli, Rosalba, Gigliotti, Casimiro Luca, Occhipinti, Sergio, Giovarelli, Mirella, Conti, Laura, Boggio, Elena, Shivakumar, Yogesh, Baldanzi, Gianluca, Malacarne, Valeria, Orilieri, Elisabetta, Cappellano, Giuseppe, Fantozzi, Roberto, Yagi, Junji, Rojo, Josè Maria, Chiocchetti, Annalisa, SBLATTERO, DANIELE, DIANZANI, Umberto, DE CONTI, LAURA, Dianzani, Chiara, Minelli, Rosalba, Gigliotti, Casimiro Luca, Occhipinti, Sergio, Giovarelli, Mirella, Conti, Laura, Boggio, Elena, Shivakumar, Yogesh, Baldanzi, Gianluca, Malacarne, Valeria, Orilieri, Elisabetta, Cappellano, Giuseppe, Fantozzi, Roberto, Sblattero, Daniele, Yagi, Junji, Rojo, Josè Maria, Chiocchetti, Annalisa, Dianzani, Umberto, and DE CONTI, Laura
- Subjects
Immunoglobulin Fc Fragment ,Lung Neoplasms ,Angiogenesis ,T cell ,Recombinant Fusion Proteins ,tumor cells ,Human Umbilical Vein Endothelial Cell ,Immunology ,Hep G2 Cell ,Mice, SCID ,Biology ,SCID ,migration ,B7h ,Matrix-Metalloproteinase inhibitors ,Metastasis ,Focal adhesion ,Inducible T-Cell Co-Stimulator Protein ,Inducible T-Cell Co-Stimulator Ligand ,Mice ,Immune system ,Cell Movement ,Mice, Inbred NOD ,medicine ,Human Umbilical Vein Endothelial Cells ,Immunology and Allergy ,Animals ,Humans ,Neoplasm Metastasis ,Hep G2 Cells ,Heterografts ,Immunoglobulin Fc Fragments ,Neoplasm Transplantation ,Animal ,medicine.disease ,Cell biology ,Lung Neoplasm ,Neoplasm Metastasi ,medicine.anatomical_structure ,Cell culture ,Cancer cell ,Inbred NOD ,Hepatocyte growth factor ,Heterograft ,medicine.drug ,Human ,Recombinant Fusion Protein - Abstract
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 CF-PAC1 cells, as well as C57BL/6 mice with B16-F10 cells. Therefore, the B7h−ICOS 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.
- Published
- 2014