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.
Document Type
Article
Publication Date
4-30-2015
Digital Object Identifier (DOI)
http://dx.doi.org/10.18632/oncotarget.3384
Funding Information
This work was supported by AIRC (Associazione Italiana Ricerca sul Cancro) grant IG11420 and BioKer srl to S.D.F., Italian Ministry for Scientific Research, projects PON01_01434 to S.D.F. and PON01_1602 to M.R., and by NIH grants DP1GM114862, R01EY022238 and R01EY024068 to J.A.
Repository Citation
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; and De Falco, Sandro, "Powerful Anti-Tumor and Anti-Angiogenic Activity of a New Anti-Vascular Endothelial Growth Factor Receptor 1 Peptide in Colorectal Cancer Models" (2015). Ophthalmology and Visual Science Faculty Publications. 10.
https://uknowledge.uky.edu/ophthalmology_facpub/10
Supplementary Figure
Notes/Citation Information
Published in Oncotarget, v. 6, no. 12, p. 10563-10576.
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