Lymphatic zip codes in premalignant lesions and tumors.
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.
Zhang
Lianglin
L
Cancer Research Center and Program in Molecular Pathology, Burnham Institute for Medical Research, La Jolla, California, USA.
Giraudo
Enrico
E
Hoffman
Jason A
JA
Hanahan
Douglas
D
Ruoslahti
Erkki
E
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
D009842:Oligopeptides; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases; C516766:Ptpn22 protein, mouse