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

Cancer Cell. 2003 Nov;4(5):383-91. doi: 10.1016/s1535-6108(03)00273-3.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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

Substances

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