Tumor-penetrating iRGD peptide inhibits metastasis.

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.

journal_name

Mol Cancer Ther

authors

Sugahara KN,Braun GB,de Mendoza TH,Kotamraju VR,French RP,Lowy AM,Teesalu T,Ruoslahti E

doi

10.1158/1535-7163.MCT-14-0366

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

120-8

issue

1

eissn

1535-7163

issn

1538-8514

pii

1535-7163.MCT-14-0366

journal_volume

14

pub_type

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