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

D2A-Ala is a synthetic peptide that has been created by introducing mutations in the original D2A sequence, 130 IQEGEEGRPKDDR 142 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 fi brosarcoma cell line, HT 1080, and a human colorectal adenocarcinoma cell line, HT 29. D2A-Ala exerts its e ff ects 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 immunode fi cient nude mice using HT 1080 and HT 29 cell lines showed that PEG-D2A-Ala signi fi cantly prevents tumour growth decreasing size, weight and density of tumours. The most e ffi cient 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 ex- pressing EGFR.