Lymphatic zip codes in premalignant lesions and tumors

Lianglin Zhang, Enrico Giraudo, Jason A. Hoffman, Douglas Hanahan, Erkki Ruoslahti

Research output: Contribution to journalArticlepeer-review

Abstract

Blood vessels in tumors are morphologically and functionally distinct from normal resting blood vessels. We probed lymphatic vessels in premalignant lesions and tumors by in vivo screening of phage-displayed peptide libraries, asking whether they too have distinctive signatures. The resulting peptides begin to define such signatures. One peptide identified the lymphatics in a human melanoma xenograft. Another recognized the lymphatics in prostate cancers but not in premalignant prostate lesions; this peptide similarly identifies human prostate cancer lymphatics. A third was selective for the lymphatics in the premalignant prostate lesions. A fourth identified the lymphatics in dysplasias and squamous carcinomas of the cervix and skin. None recognize lymphatics in normal tissues. Thus, tumor development is associated with organ- and stage-specific changes in lymphatics. Systemic treatment of mice with fusions of a lymphatic homing peptide and a proapoptotic motif reduced the number of tumor lymphatics in prostate tumor and melanoma, forecasting future lymphatic targeting agents for detection and therapeutic intervention.

Original languageEnglish
Pages (from-to)5696-5706
Number of pages11
JournalCancer Research
Volume66
Issue number11
DOIs
Publication statusPublished - Jun 1 2006

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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