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 / Cicatiello, Valeria; Apicella, Ivana; Tudisco, Laura; Tarallo, Valeria; Formisano, Luigi; Sandomenico, Annamaria; Kim, Younghee; Bastos Carvalho, Ana; Orlandi, Augusto; Ambati, Jayakrishna; Ruvo, Menotti; Bianco, Roberto; De Falco, Sandro. - In: ONCOTARGET. - ISSN 1949-2553. - 6:12(2015), pp. 10563-76-10576. [10.18632/oncotarget.3384]

Powerful anti-tumor and anti-angiogenic activity of a new anti-vascular endothelial growth factor receptor 1 peptide in colorectal cancer models

TARALLO, VALERIA;FORMISANO, LUIGI;Ruvo, Menotti;BIANCO, ROBERTO;
2015

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.
2015
Powerful anti-tumor and anti-angiogenic activity of a new anti-vascular endothelial growth factor receptor 1 peptide in colorectal cancer models / Cicatiello, Valeria; Apicella, Ivana; Tudisco, Laura; Tarallo, Valeria; Formisano, Luigi; Sandomenico, Annamaria; Kim, Younghee; Bastos Carvalho, Ana; Orlandi, Augusto; Ambati, Jayakrishna; Ruvo, Menotti; Bianco, Roberto; De Falco, Sandro. - In: ONCOTARGET. - ISSN 1949-2553. - 6:12(2015), pp. 10563-76-10576. [10.18632/oncotarget.3384]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/615672
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