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2015 ; 14
(1
): 120-8
Nephropedia Template TP
Sugahara KN
; Braun GB
; de Mendoza TH
; Kotamraju VR
; French RP
; Lowy AM
; Teesalu T
; Ruoslahti E
Mol Cancer Ther
2015[Jan]; 14
(1
): 120-8
PMID25392370
show ga
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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