Powerful anti-tumor and anti-angiogenic activity of a new anti-vascular endothelial growth factor receptor 1 peptide in colorectal cancer models(470 views) Cicatiello V, Apicella I, Tudisco L, Tarallo V, Formisano L, Sandomenico A, Kim Y, Bastos-Carvalho A, Orlandi A, Ambati J, Ruvo M, Bianco R, de Falco S
Keywords: Angiogenesis, Choroid Neovascularization, Colorectal Cancer, Metastasis, Vegfr1, Angiogenesis Inhibitor, Bevacizumab, Inhibitor Of Vasculotropin Receptor 1, Irinotecan, Unclassified Drug, Animal Cell, Animal Experiment, Animal Model, Animal Tissue, Antiangiogenic Activity, Antineoplastic Activity, Article, Cancer Combination Chemotherapy, Cancer Inhibition, Cancer Model, Cancer Prognosis, Cancer Survival, Dose Response, Drug Activity, Drug Dose Comparison, Drug Megadose, Drug Potency, Drug Potentiation, Hct116 Cell Line, Human, Human Cell, In Vitro Study, In Vivo Study, Lung Metastasis, Macrophage, Macrophage Migration Inhibition, Metastasis Inhibition, Monocyte, Mouse, Nonhuman, Pericyte, Protein Phosphorylation, Single Drug Dose, Subretinal Neovascularization, Survival Time, Treatment Duration, Treatment Outcome, Tumor Invasion, Tumor Vascularization,
Affiliations: *** IBB - CNR ***
Angiogenesis Lab, Institute of Genetics and Biophysics Adriano Buzzati-Traverso-CNR, Naples, Italy
Bio-Ker, MultiMedica Group, Napoli, Italy
Department of Clinic Medicine and Surgery, University of Naples Federico II, Italy
Institute of Biostructures and Bioimaging-CNR and CIRPeB, University of Naples Federico II, Italy
Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY, United States
Anatomic Pathology Institute, Department of Biomedicine and Prevention, Tor Vergata University of Rome, Italy
IRCCS MultiMedica, Milan, Italy
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Powerful anti-tumor and anti-angiogenic activity of a new anti-vascular endothelial growth factor receptor 1 peptide in colorectal cancer models
To assess the therapeutic outcome of selective block of VEGFR1, we have evaluated the activity of a new specific antagonist of VEGFR1, named iVR1 (inhibitor of VEGFR1), in syngenic and xenograft colorectal cancer models, in an artificial model of metastatization, and in laser-induced choroid neovascularization. iVR1 inhibited tumor growth and neoangiogenesis in both models of colorectal cancer, with an extent similar to that of bevacizumab, a monoclonal antibody anti-VEGF-A. It potently inhibited VEGFR1 phosphorylation in vivo, determining a strong inhibition of the recruitment of monocyte-macrophages and of mural cells as confirmed, in vitro, by the ability to inhibit macrophages migration. iVR1 was able to synergize with irinotecan determining a shrinkage of tumors that became undetectable after three weeks of combined treatment. Such treatment induced a significant prolongation of survival similar to that observed with bevacizumab and irinotecan combination. iVR1 also fully prevented lung invasion by HCT-116 cells injected in mouse tail vein. Also, iVR1 impressively inhibited choroid neovascularization after a single intravitreal injection. Collectively, data showed the strong potential of iVR1 peptide as a new anti-tumor and anti-metastatic agent and demonstrate the high flexibility of VEGFR1 antagonists as therapeutic anti-angiogenic agents in different pathological contexts.
Powerful anti-tumor and anti-angiogenic activity of a new anti-vascular endothelial growth factor receptor 1 peptide in colorectal cancer models
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