Methaemoglobin enhances the proliferation of transformed human epithelial cells: a possible outcome of neovascularisation and haemorrhage in tumours?

Abstract

The effect of human methaemoglobin (metHb), possibly derived from extravasated red blood cells in tumours showing neovascularisation and haemorrhage, on the growth of transformed human epithelial cells was investigated. MetHb stimulated the growth of immortalised epithelial cells or transformed cells at precrisis stage (cells have bypassed M1, but not M2, the two mortality checkpoints). The stimulatory effect was due to the release of haemin from metHb that was isolated by a Sephadex column and identified by its characteristic light absorption spectrum. Although all the degradation products of haemin are currently known to be physiologically significant, only ferric iron derived from metHb or haemin could stimulate cell growth. High concentrations of metHb or haemin inhibited cell growth possibly due to the generation of high concentrations of bilirubin. However, bilirubin formed in the cells of human body is known to be transported to the liver for further processing and excretion. Haemoglobin oxidised to where tumours show neovascularisation and haemorrhage likely contributes significantly to the increased proliferation of cancerous cells.