title: Lymphatic zip codes in premalignant lesions and tumors.
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.
authors.affiliation: Cancer Research Center and Program in Molecular Pathology, Burnham Institute for Medical Research, La Jolla, California, USA.
authors.forename: Lianglin
authors.initials: L
authors.lastname: Zhang
authors.forename: Enrico
authors.initials: E
authors.lastname: Giraudo
authors.forename: Jason A
authors.initials: JA
authors.lastname: Hoffman
authors.forename: Douglas
authors.initials: D
authors.lastname: Hanahan
authors.forename: Erkki
authors.initials: E
authors.lastname: Ruoslahti
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D008208:Lymphatic System / Q000473:pathology*; D008297:Male; D008545:Melanoma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000473:pathology; D009842:Oligopeptides / Q000378:metabolism; D011230:Precancerous Conditions / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000473:pathology; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011817:Rabbits; D012878:Skin Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D013379:Substrate Specificity; D002583:Uterine Cervical Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology
chemical_list: D009842:Oligopeptides; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases; C516766:Ptpn22 protein, mouse