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Issue 1131 coverThe Lymphatic Continuum Revisited Volume 1131 published May 2008
Ann. N.Y. Acad. Sci. 1131: 37–43 (2008). doi: 10.1196/annals.1413.003
Copyright © 2008 by the New York Academy of Sciences
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Articles by LAAKKONEN, P.
Articles by RUOSLAHTI, E.
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Articles by LAAKKONEN, P.
Articles by RUOSLAHTI, E.

Part I. Tools for Lymphatic Investigation

Peptide Targeting of Tumor Lymph Vessels

PIRJO LAAKKONENa, LIANGLIN ZHANGb AND ERKKI RUOSLAHTIc

a Molecular Cancer Biology Research Program and Institute of Biomedicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland b Cancer Research Center, Burnham Institute for Medical Research, La Jolla, California, USA c Burnham Institute for Medical Research (at UCSB), University of California, Santa Barbara, Santa Barbara, California, USA

Key Words: peptide • tumor targeting • phage display • lymphatics

Address for correspondence: Pirjo Laakkonen, Ph.D., Adjunct Professsor, Molecular Cancer Biology Research Program and Institute of Biomedicine, Biomedicum Helsinki, P.O. Box 63, Haartmaninkatu 8, 00014 University of Helsinki, Finland. Voice: +358-9-191-25537; fax: +358-9-191-25510.  pirjo.laakkonen{at}helsinki.fi

In addition to having a blood vasculature, most normal organs and pathologic conditions involve a second vascular system, the lymphatic vasculature, and many tumors induce the growth of new lymphatic vessels. However, compared to the blood vasculature, very little is known about the lymphatic vessels in tumors. We have used the in vivo phage display technology to map tumor-specific differences in the lymphatic vasculature, and identified peptides that specifically home to tumor lymphatics. Each of these peptides recognizes lymphatic vessels in a different set of tumors, and some of them also recognize tumor cells. Furthermore, these peptides can differentiate lymphatic vasculature of a premalignant lesion from that of a full-blown tumor, indicating tumor stage–specific differences in the lymphatic vessels. None of the lymphatic homing peptides recognizes blood endothelial cells, nor do they home to any normal organ. Of interest, some of our homing peptides are able to penetrate the target cells in a cell type–specific manner. These peptides appear to be able to concentrate in the target tissue, making them particularly efficient delivery vectors for the targeting of therapeutic moieties and imaging agents. Conjugation of the lymphatic homing peptides to drugs provides an opportunity to specifically deliver therapeutic agents into tumors using a route not previously exploited. The surprising degree of selectivity of these lymphatic homing peptides suggests extensive molecular specialization of tumor lymphatic vessels, positing the existence of a molecular lymphatic "zip code" system, as has been previously demonstrated for the tumor blood vasculature.






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