Peptides selected for binding to clotted plasma accumulate in tumor stroma and wounds.

作者: J. Pilch , D. M. Brown , M. Komatsu , T. A. H. Jarvinen , M. Yang

DOI: 10.1073/PNAS.0511219103

关键词: PeptideFibronectinsBiologyPhage displayExtracellularPeptide libraryFibronectinBlood proteinsMolecular biologyFibrin

摘要: Screening of a phage library for peptides that bind to clotted plasma in the presence liquid yielded two cyclic decapeptides, CGLIIQKNEC (CLT1) and CNAGESSKNC (CLT2). When injected intravenously into mice bearing various types tumors, fluorescein-conjugated CLT accumulated fibrillar meshwork extracellular compartment but were not detectable other tissues tumor-bearing mice. The tumor homing both was strongly reduced after coinjection with unlabeled CLT2, indicating recognize same binding site. peptide fluorescence colocalized staining fibrin(ogen) present extravascular tissues. did home tumors grown fibrinogen-null or lack fibronectin. also at sites injury arteries, skeletal muscle, skin. We conclude fibrin-fibronectin complexes formed by clotting proteins have leaked space lesions. These may be useful targeting diagnostic therapeutic materials injured

参考文章(28)
Joseph S. Palumbo, Keith W. Kombrinck, Angela F. Drew, Timothy S. Grimes, John H. Kiser, Jay L. Degen, Thomas H. Bugge, Fibrinogen is an important determinant of the metastatic potential of circulating tumor cells. Blood. ,vol. 96, pp. 3302- 3309 ,(2000) , 10.1182/BLOOD.V96.10.3302
DF Mosher, Cross-linking of cold-insoluble globulin by fibrin-stabilizing factor. Journal of Biological Chemistry. ,vol. 250, pp. 6614- 6621 ,(1975) , 10.1016/S0021-9258(19)41110-1
H. Michael Ellerby, Wadih Arap, Lisa M. Ellerby, Renate Kain, Rebecca Andrusiak, Gabriel Del Rio, Stanislaw Krajewski, Christian R. Lombardo, Rammohan Rao, Erkki Ruoslahti, Dale E. Bredesen, Renata Pasqualini, Anti-cancer activity of targeted pro-apoptotic peptides Nature Medicine. ,vol. 5, pp. 1032- 1038 ,(1999) , 10.1038/12469
Takao Sakai, Kamin J. Johnson, Michihiro Murozono, Keiko Sakai, Marc A. Magnuson, Tadeuz Wieloch, Tobias Cronberg, Atsushi Isshiki, Harold P. Erickson, Reinhard Fässler, Plasma fibronectin supports neuronal survival and reduces brain injury following transient focal cerebral ischemia but is not essential for skin-wound healing and hemostasis. Nature Medicine. ,vol. 7, pp. 324- 330 ,(2001) , 10.1038/85471
Joseph B. Ventimiglia, Carol J. Wikstrand, Lawrence E. Ostrowski, Mario A. Bourdon, Virginia A. Lightner, Darell D. Bigner, Tenascin expression in human glioma cell lines and normal tissues. Journal of Neuroimmunology. ,vol. 36, pp. 41- 55 ,(1992) , 10.1016/0165-5728(92)90029-K
Farouc A. Jaffer, Ching-Hsuan Tung, Joanna J. Wykrzykowska, Nan-Hui Ho, Aiilyan K. Houng, Guy L. Reed, Ralph Weissleder, Molecular imaging of factor XIIIa activity in thrombosis using a novel, near-infrared fluorescent contrast agent that covalently links to thrombi. Circulation. ,vol. 110, pp. 170- 176 ,(2004) , 10.1161/01.CIR.0000134484.11052.44
Erkki Ruoslahti, Specialization of tumour vasculature Nature Reviews Cancer. ,vol. 2, pp. 83- 90 ,(2002) , 10.1038/NRC724
H. Dvorak, D. Senger, A. Dvorak, V. Harvey, J McDonagh, Regulation of Extravascular Coagulation by Microvascular Permeability Science. ,vol. 227, pp. 1059- 1061 ,(1985) , 10.1126/SCIENCE.3975602
H Ten Cate, KA Bauer, M Levi, TS Edgington, RD Sublett, S Barzegar, BL Kass, RD Rosenberg, None, The activation of factor X and prothrombin by recombinant factor VIIa in vivo is mediated by tissue factor. Journal of Clinical Investigation. ,vol. 92, pp. 1207- 1212 ,(1993) , 10.1172/JCI116691
P. Laakkonen, M. E. Akerman, H. Biliran, M. Yang, F. Ferrer, T. Karpanen, R. M. Hoffman, E. Ruoslahti, Antitumor activity of a homing peptide that targets tumor lymphatics and tumor cells Proceedings of the National Academy of Sciences of the United States of America. ,vol. 101, pp. 9381- 9386 ,(2004) , 10.1073/PNAS.0403317101