Characterization of Receptors for Peptides Homing to the Vasculature of the Breast Carcinomas by Display Cloning
Abstract
Using in vivo screening of phage-displayed peptide libraries, a pentapeptide, CREKA, which homes to vasculature of breast tumor in mice was identified. The CREKA-displaying phage homes to breast tumors in mice with a 100-fold selectivity over non-recombinant phage. The homing of the CREKA phage was inhibited by its cognate synthetic peptide. The CREKA-displaying phage and fluorescein-labeled CREKA peptide were taken up by tumor tissue, but not by control tissues, and they co-localized with septa of connective tissue in tumors. Using the CREKA peptide in expression cloning with a phage-displayed cDNA library yielded a phage that specifically bound to the peptide. The cDNA coded for a fragment of the collagen Iv alpha 2 chain with typical Gly-X-Y repeats. CREKA phage bound avidly to immobilized collagen. Heat denaturation of the triple helical structure of collagen enhanced CREKA binding to collagen. These results indicate that the CREKA peptide homes to tumors because it binds to non-triple-helical collagen in angiogenic blood vessels. The investigation of drug-CREKA conjugate for the prevention and treatrnent of breast tumor in mice has been undergoing.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2003
- Accession Number
- ADA418117
Entities
People
- Lianglin Zhang
Organizations
- Sanford Burnham Prebys Medical Discovery Institute