Effect of hypoxia on cadherin expression in colorectal cancer

Aims: Cadherins mediate cell-cell adhesion in epithelial tissues, and in epithelial tumours loss of E-cadherin expression is associated with reduced survival and increased metastases while neo-expression of N-cadherin increases tumour invasiveness. We investigated the effect of hypoxia on cadherin expression in colorectal cancer cell lines.

Methods: Three colorectal cancer cell lines, two primary (HT-29, SW480) and one metastatic (SW1116), were cultured to near confluence and exposed to hypoxia at a level of 1% for 12, 24 or 48 hours. E-cadherin and N-cadherin expression was determined by western blot analysis and quantified by densitometry. Cadherin localisation was demonstrated by immunocytochemistry and compared by two blinded observers.

Results: The insoluble fraction of E-cadherin, which is involved in cell adhesion, was reduced with hypoxia by 35% at 12 and 40% at 24 hours by western blot analysis. Immunocytochemistry confirmed reduced membranous staining of E-cadherin with exposure to hypoxia. N-cadherin was not expressed at baseline by any of the cell lines and its expression was not induced by hypoxia.

Conclusions: E-cadherin expression was reduced in response to hypoxia in colorectal cancer cell lines. This mechanism may be involved in E-cadherin loss in vivo.