title: Powerful anti-tumor and anti-angiogenic activity of a new anti-vascular endothelial growth factor receptor 1 peptide in colorectal cancer models.
abstract: 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.
authors: Angiogenesis Lab, Institute of Genetics and Biophysics "Adriano Buzzati-Traverso" - CNR, Naples, Italy.|Bio-Ker, MultiMedica Group, Napoli, Italy.
authors: Valeria
authors: V
authors: Cicatiello
authors: Angiogenesis Lab, Institute of Genetics and Biophysics "Adriano Buzzati-Traverso" - CNR, Naples, Italy.
authors: Ivana
authors: I
authors: Apicella
authors: Angiogenesis Lab, Institute of Genetics and Biophysics "Adriano Buzzati-Traverso" - CNR, Naples, Italy.
authors: Laura
authors: L
authors: Tudisco
authors: Angiogenesis Lab, Institute of Genetics and Biophysics "Adriano Buzzati-Traverso" - CNR, Naples, Italy.
authors: Valeria
authors: V
authors: Tarallo
authors: Medical Oncology, Department of Clinic Medicine and Surgery, University of Naples "Federico II", Italy.
authors: Luigi
authors: L
authors: Formisano
authors: Institute of Biostructures and Bioimaging - CNR and CIRPeB, University of Naples "Federico II", Italy.
authors: Annamaria
authors: A
authors: Sandomenico
authors: Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, KY, USA.
authors: Younghee
authors: Y
authors: Kim
authors: Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, KY, USA.
authors: Ana
authors: A
authors: Bastos-Carvalho
authors: Anatomic Pathology Institute, Department of Biomedicine and Prevention, Tor Vergata University of Rome, Italy.
authors: Augusto
authors: A
authors: Orlandi
authors: Department of Ophthalmology & Visual Sciences, University of Kentucky, Lexington, KY, USA.
authors: Jayakrishna
authors: J
authors: Ambati
authors: Institute of Biostructures and Bioimaging - CNR and CIRPeB, University of Naples "Federico II", Italy.
authors: Menotti
authors: M
authors: Ruvo
authors: Medical Oncology, Department of Clinic Medicine and Surgery, University of Naples "Federico II", Italy.
authors: Roberto
authors: R
authors: Bianco
authors: Angiogenesis Lab, Institute of Genetics and Biophysics "Adriano Buzzati-Traverso" - CNR, Naples, Italy.|IRCCS MultiMedica, Milan, Italy.
authors: Sandro
authors: S
authors: De Falco
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D009842:Oligopeptides / Q000494:pharmacology*; D000067996:RAW 264.7 Cells; D011897:Random Allocation; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors*; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D009842:Oligopeptides; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: VEGFR1; angiogenesis; choroid neovascularization; colorectal cancer; metastasis