Lymphatic zip codes in premalignant lesions and tumors

Area of Science:

• Oncology
• Vascular Biology
• Biotechnology

Background:

• Tumor-associated blood vessels exhibit distinct characteristics compared to normal vasculature.
• The specific changes in lymphatic vessels during tumor development remain largely uncharacterized.

Purpose of the Study:

• To investigate whether lymphatic vessels in premalignant lesions and tumors possess unique molecular signatures.
• To identify novel peptides that can selectively target tumor-associated lymphatics for potential diagnostic and therapeutic applications.

Main Methods:

• In vivo screening of phage-displayed peptide libraries was employed to identify peptides that bind to lymphatic vessels.
• The identified peptides were tested for their specificity in various preclinical cancer models, including melanoma and prostate cancer xenografts, as well as premalignant lesions.
• The therapeutic potential of a lymphatic-homing peptide fused with a proapoptotic motif was evaluated in mouse models.

Main Results:

• Distinct peptide signatures were identified for tumor-associated lymphatic vessels, differing from those in normal tissues.
• Specific peptides were found to selectively target lymphatics in melanoma, prostate cancer, cervical dysplasia, and squamous carcinomas.
• One peptide differentiated between premalignant prostate lesions and established prostate cancer lymphatics.
• Systemic administration of a peptide-drug conjugate reduced tumor lymphatic density in prostate and melanoma models.

Conclusions:

• Tumorigenesis is associated with organ- and stage-specific alterations in lymphatic vessel signatures.
• The identified peptides represent promising tools for the development of novel diagnostic and therapeutic agents targeting tumor lymphatics.
• Targeting tumor lymphatics holds potential for future cancer detection and intervention strategies.