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Tumor-Penetrating iRGD Peptide Inhibits Metastasis

Year: 2014
Type: article
Abstract: 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.
DOI: 10.1158/1535-7163.mct-14-0366
Authors: Kazuki N. Sugahara, Gary B. Braun, Tatiana Hurtado de Mendoza, Venkata Ramana Kotamraju, Randall P. French, Andrew M. Lowy, Tambet Teesalu, Erkki Ruoslahti
Institutions: Sanford Burnham Prebys Medical Discovery Institute, Columbia University Irving Medical Center, Columbia University, University of California, Santa Barbara, University of California San Diego, Moores Cancer Center, University of Tartu
Language: English
Field: Medicine
Open Access status: green
Awards: G1020269591, The role of fibroblasts in the activities of tissue penetrating peptides, Development of tissue penetrating peptides for targeted drug delivery., Trans-disciplinary Postdoctoral Training in Cancer Biology, G4657894719, Tumor Penetrating Peptides for Cancer Targeting, G8632904647, Cancer Center Support Grant (CCSG)
OpenAlex ID: W2120353663
FWCI: 9.732
Cites: 45
Cited by: 135
Related to: 10