RT Journal Article
SR Electronic
T1 Tumor-Penetrating iRGD Peptide Inhibits Metastasis
JF Molecular Cancer Therapeutics
JO Mol Cancer Ther
FD American Association for Cancer Research
SP 120
OP 128
DO 10.1158/1535-7163.MCT-14-0366
VO 14
IS 1
A1 Sugahara, Kazuki N.
A1 Braun, Gary B.
A1 de Mendoza, Tatiana Hurtado
A1 Kotamraju, Venkata Ramana
A1 French, Randall P.
A1 Lowy, Andrew M.
A1 Teesalu, Tambet
A1 Ruoslahti, Erkki
YR 2015
UL http://mct.aacrjournals.org/content/14/1/120.abstract
AB Tumor-specific tissue-penetrating peptides deliver drugs into extravascular tumor tissue by increasing tumor vascular permeability through interaction with neuropilin (NRP). Here, we report that a prototypic tumor-penetrating peptide iRGD (amino acid sequence: CRGDKGPDC) potently inhibits spontaneous metastasis in mice. The antimetastatic effect was mediated by the NRP-binding RXXK peptide motif (CendR motif), and not by the integrin-binding RGD motif. iRGD inhibited migration of tumor cells and caused chemorepulsion in vitro in a CendR- and NRP-1–dependent manner. The peptide induced dramatic collapse of cellular processes and partial cell detachment, resulting in the repellent activity. These effects were prominently displayed when the cells were seeded on fibronectin, suggesting a role of CendR in functional regulation of integrins. The antimetastatic activity of iRGD may provide a significant additional benefit when this peptide is used for drug delivery to tumors. Mol Cancer Ther; 14(1); 120–8. ©2014 AACR.