Cellularly generated active oxygen species as signals in the activation of tumour cell growth

Summary

It has become clear that superoxide and hydrogen peroxide at low levels can stimulate growth, or growth responses, in a variety of normal and tumour cell types when added exogenously. It is also evident that these active oxygen species are released from, or generated within, most of these cell types. Whereas ‘normal’ cells appear to require the stimulus of serum factors or phorbol esters, tumour cells seem to release superoxide constitutively. Experiemnts with extracellularly added superoxide dismutase and catalase suggest that superoxide radicals and hydrogen peroxide may have important biological roles in intra- and intercellular ‘messengers’, or ‘signals’, promoting cell proliferation and maintaining cell viability.

With regard to possible mechanisms, suggestions have been made that superoxide, and hydrogen peroxide, might function as mitogenic stimuli through biochemical processes common to cell growth factors. It is possible that they ‘signal’ by covalent modification of key cellular growth regulatory proteins on the basis of redox potenital, thus setting redox states appropriate fo cell growth responses. Altenatively they may oxidatively inactivate extracellular proteases thereby facilitating normal growth factor signalling. In the case of tumour cells reduced levels of antioxidant enzymes may more readily permit them to adjust their redox status in such a way that growth signal pathways are continuously in an up-regulated state.