Angiogenesis in potentially malignant lesions and carcinomas during experimental oral carcinogenesis: a preliminary study in the hamster cheek pouch

Anticancer Res. 2014 Nov;34(11):6381-8.

Abstract

Aim: To evaluate vascular morphology and density, angiogenic switch activation, vascular endothelial growth factor (VEGF) expression, and endothelial cell (EC) proliferation in the hamster cheek pouch (HCP) model of oral cancer.

Materials and methods: Immunohistochemical detection of factor VIII, 5'-Bromo-2'-Deoxyuridine (BrdU) and VEGF was performed in pre-malignant and tumoral tissues.

Results: Activation of angiogenesis was detected adjacent to epithelial dysplasia. Vascularized area and perimeter (p<0.001) increased in dysplasias and tumors. Tumor blood vessels exhibited an enhanced vascular compression (p<0.001) and structural alterations. EC proliferation was similar in dysplasias and carcinomas. An increase in vascular density, EC proliferation and VEGF expression was found in potentially malignant tissues but not in carcinomas.

Conclusion: The angiogenic switch occurs in the dysplastic stage preceding tumor development in the HCP model of oral cancer. In potentially malignant tissues, increased VEGF expression favors EC proliferation and an increase in vascular density. Conversely, in tumors, VEGF is no longer of pivotal importance.

Keywords: Experimental carcinogenesis; angiogenesis; angiogenic switch; hamster cheek pouch; microvasculature; oral cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / toxicity
  • Animals
  • Apoptosis
  • Biomarkers, Tumor / metabolism
  • Carcinogens / toxicity
  • Cell Proliferation
  • Cheek / pathology*
  • Cricetinae
  • Disease Models, Animal
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology*
  • Immunoenzyme Techniques
  • Mesocricetus
  • Mouth Neoplasms / blood supply*
  • Mouth Neoplasms / chemically induced
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology*
  • Neovascularization, Pathologic / pathology*
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Biomarkers, Tumor
  • Carcinogens
  • Vascular Endothelial Growth Factor A
  • 9,10-Dimethyl-1,2-benzanthracene