Progressive vascular changes in a transgenic mouse model of squamous cell carcinoma.
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.
Hoffman
Jason A
JA
Cancer Research Center, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Giraudo
Enrico
E
Singh
Mallika
M
Zhang
Lianglin
L
Inoue
Masahiro
M
Porkka
Kimmo
K
Hanahan
Douglas
D
Ruoslahti
Erkki
E
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism* / Q000503:physiopathology; D002294:Carcinoma, Squamous Cell / Q000098:blood supply* / Q000235:genetics / Q000473:pathology; D004476:Ectodermal Dysplasia / Q000378:metabolism / Q000503:physiopathology; D006497:Heparan Sulfate / Q000378:metabolism*; D007150:Immunohistochemistry; D007610:Kallikreins / Q000378:metabolism*; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics*; D019151:Peptide Library; D010455:Peptides / Q000235:genetics* / Q000378:metabolism; D012867:Skin / Q000378:metabolism* / Q000503:physiopathology
D006497:Heparan Sulfate; D007610:Kallikreins; D009363:Neoplasm Proteins; D019151:Peptide Library; D010455:Peptides; C410801:KLK9 protein, human