Progressive vascular changes in a transgenic mouse model of squamous cell carcinoma.

Abstract

Phage display was used to identify homing peptides for blood vessels in a mouse model of HPV16-induced epidermal carcinogenesis. One peptide, CSRPRRSEC, recognized the neovasculature in dysplastic skin but not in carcinomas. Two other peptides, with the sequences CGKRK and CDTRL, preferentially homed to neovasculature in tumors and, to a lesser extent, premalignant dysplasias. The peptides did not home to vessels in normal skin, other normal organs, or the stages in pancreatic islet carcinogenesis in another mouse model. The CGKRK peptide may recognize heparan sulfates in tumor vessels. The dysplasia-homing peptide is identical to a loop in kallikrein-9 and may bind a kallikrein inhibitor or substrate. Thus, characteristics of the angiogenic vasculature distinguish premalignant and malignant stages of skin tumorigenesis.

• Authors: Jason A Hoffman, Enrico Giraudo, Mallika Singh, Lianglin Zhang, Masahiro Inoue, Kimmo Porkka, Douglas Hanahan, Erkki Ruoslahti
• Journal: Cancer cell (Cancer Cell) Vol. 4 Issue 5 Pg. 383-91 (Nov 2003) ISSN: 1535-6108 [Print] United States
• PMID: 14667505 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Neoplasm Proteins
• Peptide Library
• Peptides
• Heparitin Sulfate
• KLK9 protein, human
• Kallikreins

Topics

• Animals
• Blood Vessels (metabolism, physiopathology)
• Carcinoma, Squamous Cell (blood supply, genetics, pathology)
• Ectodermal Dysplasia (metabolism, physiopathology)
• Heparitin Sulfate (metabolism)
• Immunohistochemistry
• Kallikreins (metabolism)
• Mice
• Neoplasm Proteins (metabolism)
• Neoplasm Staging
• Neovascularization, Pathologic (genetics)
• Peptide Library
• Peptides (genetics, metabolism)
• Skin (metabolism, physiopathology)