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


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
Issue number11
Publication statusPublished - Jun 1 2006

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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