Efficient In Vivo Selection of a Novel Tumor-Associated Peptide from a Phage Display Library.docVIP

Molecules 2011, 16, 900-914; doi:10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Efficient In Vivo Selection of a Novel Tumor-Associated Peptide from a Phage Display Library Anka N. Veleva 1,2,*, Desh B. Nepal 2, C. Brandon Frederick 1,3, Jacob Schwab 2, Pamela Lockyer 2, Hong Yuan 3, David S. Lalush 1,3 and Cam Patterson 2,4,5,6 1 Department of Biomedical Engineering, North Carolina State University, Raleigh, NC 27695, USA; E-Mails: cbfreder@ (C.B.F.); dslalush@ (D.S.L.) 2 McAllister Heart Institute, University of North Carolina, Chapel Hill, NC 27599, USA; E-Mails: dbnepal@ (D.B.N.); schwab.jacob@ (J.S.); plockyer@ (P.L.); cpatters@ (C.P.) 3 Biomedical Research Imaging Center, University of North Carolina, Chapel Hill, NC 27599, USA; E-Mail: yuanh@ (H.Y.) 4 Department of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA 5 Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, NC 27599, USA 6 Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA * Author to whom correspondence should be addressed; E-Mail: anveleva@; Tel.: +1-919-515-1271. Received: 15 December 2010; in revised form: 14 January 2011 / Accepted: 18 January 2011 / Published: 21 January 2011 Abstract: We developed a screening procedure to identify ligands from a phage display random peptide library that are selective for circulating bone marrow derived cells homing to angiogenic tumors. Panning the library on blood outgrowth endothelial cell suspension in vitro followed by in vivo selection based on homing of bone marrow-bound phage to angiogenic tumors, yielded the peptide QFPPKLTNNSML. Upon intravenous injection phage displaying this peptide homed to Lewis lung carcinoma (LLC) tumors in vivo whereas control phage did not localize to tumor tissue. Phage carrying the QFPPKLTNNSML peptide labeled wit