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Tumor-penetrating iRGD peptide inhibits metastasis.

Authors
Type
Published Article
Journal
Molecular Cancer Therapeutics
Publisher
American Association for Cancer Research
Volume
14
Issue
1
Pages
120–128
Identifiers
DOI: 10.1158/1535-7163.MCT-14-0366
Source
Ruoslahti Lab
License
Unknown

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.

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