D2A-Ala is a synthetic peptide that has been created by introducing mutations in the original D2A sequence, 130IQEGEEGRPKDDR142 of human urokinase receptor (uPAR). In vitro, D2A-Ala peptide displays strong anti-tumoural properties inhibiting EGF-induced chemotaxis, invasion and proliferation of a human fibrosarcoma cell line, HT 1080, and a human colorectal adenocarcinoma cell line, HT 29. D2A-Ala exerts its effects by preventing EGF receptor (EGFR) phosphorylation. To test D2A-Ala in vivo, this peptide was PEGylated generating polyethyleneglycol (PEG)-D2A-Ala peptide. PEGylation did not alter the inhibitory properties of D2A-Ala. Human tumour xenografts in the immunodeficient nude mice using HT 1080 and HT 29 cell lines showed that PEG-D2A-Ala significantly prevents tumour growth decreasing size, weight and density of tumours. The most efficient doses of the peptide were 5 and 10 mg/kg, thereby relevant for possible development of the peptide into a drug against cancer in particular tumours expressing EGFR.

D2A-Ala peptide derived from the urokinase receptor exerts anti-tumoural effects in vitro and in vivo / F. Furlan, G. Eden, M. Archinti, R. Arnaudova, G. Andreotti, V. Citro, M.V. Cubellis, A. Motta, B. Degryse. - In: PEPTIDES. - ISSN 0196-9781. - 101(2018 Mar), pp. 17-24. [10.1016/j.peptides.2017.12.016]

D2A-Ala peptide derived from the urokinase receptor exerts anti-tumoural effects in vitro and in vivo

V. Citro;
2018-03

Abstract

D2A-Ala is a synthetic peptide that has been created by introducing mutations in the original D2A sequence, 130IQEGEEGRPKDDR142 of human urokinase receptor (uPAR). In vitro, D2A-Ala peptide displays strong anti-tumoural properties inhibiting EGF-induced chemotaxis, invasion and proliferation of a human fibrosarcoma cell line, HT 1080, and a human colorectal adenocarcinoma cell line, HT 29. D2A-Ala exerts its effects by preventing EGF receptor (EGFR) phosphorylation. To test D2A-Ala in vivo, this peptide was PEGylated generating polyethyleneglycol (PEG)-D2A-Ala peptide. PEGylation did not alter the inhibitory properties of D2A-Ala. Human tumour xenografts in the immunodeficient nude mice using HT 1080 and HT 29 cell lines showed that PEG-D2A-Ala significantly prevents tumour growth decreasing size, weight and density of tumours. The most efficient doses of the peptide were 5 and 10 mg/kg, thereby relevant for possible development of the peptide into a drug against cancer in particular tumours expressing EGFR.
Cancer; Cell migration; Cell proliferation; EGF receptor; Tumour growth; Urokinase receptor; Adenosarcoma; Animals; Antineoplastic Agents; Chemotaxis; Colorectal Neoplasms; Female; Fibrosarcoma; HT29 Cells; Humans; Mice; Mice, Nude; Neoplasm Invasiveness; Oligopeptides; Receptors, Urokinase Plasminogen Activator; Xenograft Model Antitumor Assays
Settore BIO/10 - Biochimica
Settore MED/04 - Patologia Generale
Settore BIO/11 - Biologia Molecolare
Settore BIO/13 - Biologia Applicata
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/724678
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