Tumor-penetrating iRGD peptide inhibits metastasis.
Tumor-penetrating iRGD peptide inhibits metastasis.
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DOI：
10.1158/1535-7163.mct-14-0366
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发表时间：
2015-01
影响因子：
5.7
通讯作者：
Ruoslahti E
中科院分区：
文献类型：
--
作者：
Sugahara KN;Braun GB;de Mendoza TH;Kotamraju VR;French RP;Lowy AM;Teesalu T;Ruoslahti E
肿瘤特异性组织穿透肽通过与神经匹林（neuropilin， NRP）相互作用增加肿瘤血管通透性，将药物输送到血管外肿瘤组织。在这里，我们报道了一种原型肿瘤穿透肽iRGD（氨基酸序列：CRGDKGPDC）有效抑制小鼠的自发转移。抗转移作用是由nrp结合的RXXK肽基序（CendR基序）介导的，而不是由整合素结合的RGD基序介导的。在体外实验中，iRGD以依赖CendR-和nrp -1的方式抑制肿瘤细胞的迁移并引起化学排斥。肽诱导细胞过程的急剧崩溃和部分细胞脱离，导致排斥活性。当细胞被植入纤维连接蛋白时，这些作用被显著地显示出来，这表明CendR在整合素的功能调节中起作用。当iRGD用于给药时，其抗转移活性可能提供显著的额外益处。
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 anti-metastatic 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 anti-metastatic activity of iRGD may provide a significant additional benefit when this peptide is used for drug delivery to tumors.