Abstract
Each normal organ and pathological condition expresses a distinct set of molecules on their vasculature. These molecular signatures have been efficiently profiled using in vivo phage display technology. Using this technology, several peptides homing specifically to tumour blood vessels, lymphatic vessels, and/or tumour cells as well as to various normal organs have been isolated. Peptides homing to specific vascular addresses have revealed novel tissue-specific biomarkers of the normal and diseased vasculature. Tumour homing peptides have been successfully used to target therapies and imaging agents to tumours. In this review, we describe experimental setup for a combined ex vivo and in vivo screening procedure to select peptides homing to tumours.
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References
Ruoslahti, E. (2002) Specialization of tumour vasculature. Nat Rev Cancer 2, 83–90.
St Croix, B., Rago, C., Velculescu, V., Traverso, G., Romans, K.E., Montgomery, E., Lal, A., Riggins, G.J., Lengauer, C., Vogelstein, B., and Kinzler, K.W. (2000) Genes expressed in human tumor endothelium. Science 289, 1197–1202.
Oh, P., Li, Y., Yu, J., Durr, E., Krasinska, K.M., Carver, L.A., Testa, J.E., and Schnitzer, J.E. (2004) Subtractive proteomic mapping of the endothelial surface in lung and solid tumours for tissue-specific therapy. Nature 429, 629–35.
Zhang, L., Hoffman, J.A., and Ruoslahti, E. (2005) Molecular profiling of heart endothelial cells. Circulation 112, 1601–11.
Arap, W., Haedicke, W., Bernasconi, M., Kain, R., Rajotte, D., Krajewski, S., Ellerby, H.M., Bredesen, D.E., Pasqualini, R., and Ruoslahti, E. (2002) Targeting the prostate for destruction through a vascular address. Proc Natl Acad Sci USA 99, 1527–31.
Rajotte, D., Arap, W., Hagedorn, M., Koivunen, E., Pasqualini, R., and Ruoslahti, E. (1998) Molecular heterogeneity of the vascular endothelium revealed by in vivo phage display. J Clin Invest 102, 430–37.
Pasqualini, R. and Ruoslahti, E. (1996) Organ targeting in vivo using phage display peptide libraries. Nature 380, 364–66.
Porkka, K., Laakkonen, P., Hoffman, J.A., Bernasconi, M., and Ruoslahti, E. (2002) A fragment of the HMGN2 protein homes to the nuclei of tumor cells and tumor endothelial cells in vivo. Proc Natl Acad Sci USA 99, 7444–49.
Laakkonen, P., Porkka, K., Hoffman, J.A., and Ruoslahti, E. (2002) A tumor-homing peptide with a targeting specificity related to lymphatic vessels. Nat Med 8, 751–55.
Pasqualini, R., Koivunen, E., and Ruoslahti, E. (1997) Alpha v integrins as receptors for tumor targeting by circulating ligands. Nat Biotechnol 15, 542–46.
Burg, M.A., Pasqualini, R., Arap, W., Ruoslahti, E., and Stallcup, W.B. (1999) NG2 proteoglycan-binding peptides target tumor neovasculature. Cancer Res 59, 2869–74.
Gerlag, D.M., Borges, E., Tak, P.P., Ellerby, H.M., Bredesen, D.E., Pasqualini, R., Ruoslahti, E., and Firestein, G.S. (2001) Suppression of murine collagen-induced arthritis by targeted apoptosis of synovial neovasculature. Arthritis Res 3, 357–61.
Joyce, J.A., Laakkonen, P., Bernasconi, M., Bergers, G., Ruoslahti, E., and Hanahan, D. (2003) Stage-specific vascular markers revealed by phage display in a mouse model of pancreatic islet tumorigenesis. Cancer Cell 4, 393–403.
Hoffman, J.A., Giraudo, E., Singh, M., Zhang, L., Inoue, M., Porkka, K., Hanahan, D., and Ruoslahti, E. (2003) Progressive vascular changes in a transgenic mouse model of squamous cell carcinoma. Cancer Cell 4, 383–91.
Laakkonen, P., Zhang, L., and Ruoslahti, E. (2008) Peptide targeting of tumor lymph vessels. Ann N Y Acad Sci 1131, 37–43.
Enback, J. and Laakkonen, P. (2007) Tumour-homing peptides: tools for targeting, imaging and destruction. Biochem Soc Trans 35, 780–83.
Yin, H., Moulton, H.M., Betts, C., Seow, Y., Boutilier, J., Iverson, P.L., and Wood, M.J. (2009) A fusion peptide directs enhanced systemic dystrophin exon skipping and functional restoration in dystrophin-deficient mdx mice. Hum Mol Genet 18, 4405–14.
Smith, G.P. and Scott, J.K. (1993) Libraries of peptides and proteins displayed on filamentous phage. Methods Enzymol 217, 228–57.
Hoogenboom, H.R. (2002) Overview of antibody phage-display technology and its applications. Methods Mol Biol 178, 1–37.
Hoffman, J.A., Laakkonen, P., Porkka, K., Bernasconi, M., and Ruoslahti, E. (2004) In vivo and ex vivo selections using phage-displayed libraries In: Phage Display: A Practical Approach, Clarkson, T. and Lowman, H. eds (Oxford University Press, Oxford), 171–92.
Acknowledgments
This study was funded by the Finnish Cancer Organizations and the Academy of Finland as well as by research collaboration with the Marina Biotech.
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Rivinoja, A., Laakkonen, P. (2011). Identification of Homing Peptides Using the In Vivo Phage Display Technology. In: Langel, Ü. (eds) Cell-Penetrating Peptides. Methods in Molecular Biology, vol 683. Humana Press. https://doi.org/10.1007/978-1-60761-919-2_29
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DOI: https://doi.org/10.1007/978-1-60761-919-2_29
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