B7h triggering inhibits the migration of tumor cell lines
Autor: | 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 |
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Přispěvatelé: | 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, DE CONTI, Laura |
Rok vydání: | 2014 |
Předmět: |
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 |
Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 192(10) |
ISSN: | 1550-6606 |
Popis: | 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. |
Databáze: | OpenAIRE |
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