Hypoxia facilitates tumour cell detachment by reducing expression of surface adhesion molecules and adhesion to extracellular matrices without loss of cell viability

The effects of acute hypoxia on integrin expression and adhesion to extrace llular matrix proteins were investigated in two human melanoma cell lines, HMB-2 and DX3, and a human adenocarcinoma cell line, HT29. Exposure to hypo xia caused a significant downregulation of cell surface integrins and an as sociated decrease in cell adhesion. Loss of cell adhesion and integrin expr ession were transient and levels returned to normal within 24 h of reoxygen ation. Other cell adhesion molecules, such as CD44 and N-CAM, were also dow nregulated after exposure of cells to hypoxia. Acute exposure to hypoxia of cells at confluence caused rapid cell detachment. Cell detachment preceded loss of viability. Detached HMB-2 and DX3 cells completely recovered upon reoxygenation, and floating cells re-attached and continued to grow irrespe ctive of whether they were left in the original glass dishes or transferred to new culture vessels, while detached HT29 cells partly recovered upon re oxygenation. Cell detachment after decreased adhesion appears to be a stres s response, which may be a factor enabling malignant cells to escape hypoxi a in vivo, with the potential to form new foci of tumour growth.