Abstract LB-102: A tumor-specific tissue penetrating peptide inhibits metastasis

摘要: Proceedings: AACR Annual Meeting 2014; April 5-9, San Diego, CA Neuropilin-binding tumor-penetrating peptides increase vascular and tissue permeability in tumors, allowing drugs conjugated to the peptide even free co-injected with widely distribute within tumor (Sugahara KN et al, Cancer Cell 16:510, 2009; Science 328:1031, 2010). Thus, provide an elegant way enhance therapeutic index of anti-cancer drugs. However, ability has raised concerns that might metastasis by promoting cell seeding from primary tumor. Here, we show a recent unexpected finding prototypic peptide, iRGD (amino acid sequence: CRGDK/RGPD/EC), is potent inhibitor. did not cause systemic dissemination or mice bearing breast tumors low metastatic potential. treatment aggressive orthotopic pancreatic resulted significant decrease spontaneous formation. Primary growth was affected treatment. Another iNGR, also inhibited metastasis, while conventional RGD scrambled lack neuropilin affinity failed do. These results indicate anti-metastatic effect dependent on its neuropilin-binding motif. In vitro migration assays demonstrated potently inhibits serves as chemorepellent cells neuropilin-dependent manner. Chemorepulsion based live imaging confirmed findings, further dramatically collapses protrusions leading instantaneous retraction iRGD-bound surfaces. Our refutes hypothesis may enhanced metastasis. The mechanism involve neuropilin-mediated chemorepulsion cells. Collectively, simultaneously achieve tumor-specific drug delivery inhibition when utilized for cancer treatment. Citation Format: Kazuki N. Sugahara, Gary B. Braun, Tatiana H. de Mendoza, Venkata R. Kotamraju, Tambet Teesalu, Erkki Ruoslahti, Randall P. French, Andrew M. Lowy. A penetrating [abstract]. In: Proceedings 105th American Association Research; 2014 Apr 5-9; CA. Philadelphia (PA): AACR; Res 2014;74(19 Suppl):Abstract nr LB-102. doi:10.1158/1538-7445.AM2014-LB-102