Lacking hypoxia-mediated downregulation of E-cadherin in cancers of the uterine cervix

Br J Cancer. 2013 Feb 5;108(2):402-8. doi: 10.1038/bjc.2012.570. Epub 2013 Jan 15.

Abstract

Background: Experimental studies have established a causal connection between tumour hypoxia, hypoxia-associated proteome changes and downregulation of E-cadherin, the final common pathway of epithelial-to-mesenchymal transition (EMT). Our study aimed at elucidating the interrelationship of these processes in cancers of the uterine cervix in vivo.

Methods: Tumour oxygenation was assessed in 48 squamous cell carcinomas (SCC) of the uterine cervix using polarographic needle electrodes. The expression pattern of E-cadherin was investigated by immunohistochemistry and western blotting, and was compared with that of the hypoxia-inducible proteins glucose transporter (GLUT)-1 and carbonic anhydrase (CA) IX in biopsy specimens of the oxygenation measurement tracks.

Results: The majority of cervical cancers (52%) were E-cadherin positive, with a complete absence of the antigen in only 10% of the tumours. No correlation was found between the level of E-cadherin expression and the oxygenation status (mean pO(2), median pO(2) and hypoxic fractions). In patients showing partial expression of E-cadherin (38%), staining was not preferentially diminished in GLUT-1- or CA IX-positive areas, and loss of E-cadherin occurred independently of tumour cell scattering.

Conclusion: Our data provide no evidence in favour of a hypoxia-induced EMT as a mechanistic basis of cervical cancer invasiveness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / metabolism
  • Biomarkers, Tumor / metabolism
  • Cadherins / metabolism*
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases / metabolism
  • Carcinoma, Squamous Cell / metabolism
  • Cell Hypoxia*
  • Cervix Uteri / metabolism
  • Cervix Uteri / pathology
  • Down-Regulation
  • Epithelial-Mesenchymal Transition*
  • Female
  • Glucose Transporter Type 1 / metabolism
  • Humans
  • Ki-67 Antigen / metabolism
  • Middle Aged
  • Uterine Cervical Neoplasms / metabolism*

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Cadherins
  • Glucose Transporter Type 1
  • Ki-67 Antigen
  • SLC2A1 protein, human
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases