Tumor-penetrating iRGD peptide inhibits metastasis.

TitleTumor-penetrating iRGD peptide inhibits metastasis.
Publication TypeJournal Article
Year of Publication2015
AuthorsSugahara KN, Braun GB, de Mendoza THurtado, Kotamraju VRamana, French RP, Lowy AM, Teesalu T, Ruoslahti E
JournalMol Cancer Ther
Volume14
Issue1
Pagination120-8
Date Published2015 Jan
ISSN1538-8514
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.

DOI10.1158/1535-7163.MCT-14-0366
Alternate JournalMol. Cancer Ther.
PubMed ID25392370
PubMed Central IDPMC4297196
Grant List095077 / / Wellcome Trust / United Kingdom
281910 / / European Research Council / International
CA121949 / CA / NCI NIH HHS / United States
R01 CA152327 / CA / NCI NIH HHS / United States
R01 CA167174 / CA / NCI NIH HHS / United States
R01CA152327 / CA / NCI NIH HHS / United States
R01CA167174 / CA / NCI NIH HHS / United States
WT095077MA / / Wellcome Trust / United Kingdom