Format

Send to

Choose Destination
Mol Cancer Ther. 2015 Jan;14(1):120-8. doi: 10.1158/1535-7163.MCT-14-0366. Epub 2014 Nov 12.

Tumor-penetrating iRGD peptide inhibits metastasis.

Author information

1
Cancer Research Center, Sanford-Burnham Medical Research Institute, La Jolla, California. Department of Surgery, Columbia University College of Physicians and Surgeons, New York, New York. sugahara@sanfordburnham.org.
2
Cancer Research Center, Sanford-Burnham Medical Research Institute, La Jolla, California. Center for Nanomedicine and Department of Cell, Molecular and Developmental Biology, University of California Santa Barbara, Santa Barbara, California.
3
Cancer Research Center, Sanford-Burnham Medical Research Institute, La Jolla, California.
4
Division of Surgical Oncology and Moores Cancer Center, University of California, San Diego, La Jolla, California.
5
Cancer Research Center, Sanford-Burnham Medical Research Institute, La Jolla, California. Centre of Excellence for Translational Medicine, University of Tartu, Tartu, Estonia.

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.

PMID:
25392370
PMCID:
PMC4297196
DOI:
10.1158/1535-7163.MCT-14-0366
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center