Antitumor activity of a novel anti-vascular endothelial growth factor receptor-1 monoclonal antibody that does not interfere with ligand binding
| Autor: | Pedro Miguel Lacal, Stefania D'Atri, Veronica Morea, Cristina Maria Failla, Elena Bonanno, Manuel Scimeca, Grazia Graziani, Federica Ruffini, Maria Grazia Atzori, Annalisa Susanna Dorio, Lucio Tentori |
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| Rok vydání: | 2016 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A 0301 basic medicine Angiogenesis Melanoma Experimental Angiogenesis Inhibitors Ligands Monocytes Mice angiogenesis chemistry.chemical_compound Antineoplastic Agents Immunological 0302 clinical medicine Cell Movement Medicine Phosphorylation Receptor Neovascularization Pathologic Melanoma Settore BIO/14 monocyte/macrophage Vascular endothelial growth factor Endothelial stem cell medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Female Tyrosine kinase Protein Binding Research Paper VEGFR-1 03 medical and health sciences Cell Line Tumor Human Umbilical Vein Endothelial Cells melanoma Animals Humans PlGF Vasculogenic mimicry Vascular Endothelial Growth Factor Receptor-1 business.industry Macrophages Monocyte Membrane Proteins Hematopoietic Stem Cells medicine.disease Disease Models Animal 030104 developmental biology chemistry Immunology Cancer research Protein Multimerization business |
| Zdroj: | Oncotarget Oncotarget 7 (2016): 72868–72885. doi:10.18632/oncotarget.12108 info:cnr-pdr/source/autori:Graziani, Grazia; Ruffini, Federica; Tentori, Lucio; Scimeca, Manuel; Dorio, Annalisa S.; Atzori, Maria Grazia; Failla, Cristina M.; Morea, Veronica; Bonanno, Elena; D'Atri, Stefania; Lacal, Pedro M./titolo:Antitumor activity of a novel anti-vascular endothelial growth factor receptor-1 monoclonal antibody that does not interfere with ligand binding/doi:10.18632%2Foncotarget.12108/rivista:Oncotarget/anno:2016/pagina_da:72868/pagina_a:72885/intervallo_pagine:72868–72885/volume:7 |
| ISSN: | 1949-2553 |
| Popis: | Vascular endothelial growth factor receptor-1 (VEGFR-1) is a tyrosine kinase transmembrane receptor that has also a soluble isoform containing most of the extracellular ligand binding domain (sVEGFR-1). VEGF-A binds to both VEGFR-2 and VEGFR-1, whereas placenta growth factor (PlGF) interacts exclusively with VEGFR-1. In this study we generated an anti-VEGFR-1 mAb (D16F7) by immunizing BALB/C mice with a peptide that we had previously reported to inhibit angiogenesis and endothelial cell migration induced by PlGF. D16F7 did not affect binding of VEGF-A or PlGF to VEGFR-1, thus allowing sVEGFR-1 to act as decoy receptor for these growth factors, but it hampered receptor homodimerization and activation. D16F7 inhibited both the chemotactic response of human endothelial, myelomonocytic and melanoma cells to VEGFR-1 ligands and vasculogenic mimicry by tumor cells. Moreover, D16F7 exerted in vivo antiangiogenic effects in a matrigel plug assay. Importantly, D16F7 inhibited tumor growth and was well tolerated by B6D2F1 mice injected with syngeneic B16F10 melanoma cells. The antitumor effect was associated with melanoma cell apoptosis, vascular abnormalities and decrease of both monocyte/macrophage infiltration and myeloid progenitor mobilization. For all the above, D16F7 may be exploited in the therapy of metastatic melanoma and other tumors or pathological conditions involving VEGFR-1 activation. |
| Databáze: | OpenAIRE |
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