Lymphatic zip codes in premalignant lesions and tumors

• Published in: Cancer research (Chicago, Ill.) Ill.), 2006-06, Vol.66 (11), p.5696-5706
• Main Authors: LIANGLIN ZHANG, GIRAUDO, Enrico, HOFFMAN, Jason A, HANAHAN, Douglas, RUOSLAHTI, Erkki
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Female; Humans; Lymphatic System - pathology; Male; Medical sciences; Melanoma - blood supply; Melanoma - metabolism; Melanoma - pathology; Mice; Mice, Inbred C57BL; Neoplasms - blood supply; Neoplasms - metabolism; Neoplasms - pathology; Neovascularization, Pathologic - pathology; Oligopeptides - metabolism; Pharmacology. Drug treatments; Precancerous Conditions - blood supply; Precancerous Conditions - metabolism; Precancerous Conditions - pathology; Prostatic Neoplasms - blood supply; Prostatic Neoplasms - pathology; Protein Tyrosine Phosphatase, Non-Receptor Type 22; Protein Tyrosine Phosphatases - metabolism; Rabbits; Skin Neoplasms - blood supply; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; Substrate Specificity; Tumors; Uterine Cervical Neoplasms - blood supply; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - pathology
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-05-3876

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.