The role of superoxide anions in the development of distant tumour recurrence.

We hypothesise that reactive oxygen species (ROS) released from activated polymorphonuclear leucocytes during surgery play a crucial role in enhanced tumour recurrence seen after surgery. Therefore, the effect of ROS on adhesion of tumour cells to microvascular endothelium in a reproducible human in vitro model was studied. Preincubation of microvascular endothelial cells with the superoxide anion producing xanthine-xanthine oxidase complex significantly increased adhesion of the human colon carcinoma cells HT29 (167% vs control, P < 0.01), Caco2 (164% vs control, P < 0.01) and of the pancreas carcinoma cells PanC1 (180% vs control, P < 0.01). Addition of the antioxidant enzymes superoxide dismutase or catalase significantly decreased tumour cell adhesion (P < 0.01). Exposure of endothelial cells to superoxide anions increased the apoptotic rate to 7.9 times the normal rate. Additionally, exposure increased expression of the endothelial adhesion molecules E-Selectin, ICAM-1, and VCAM-1 of maximally 170% vs control (P < 0.01). In conclusion, this study shows that superoxide anions promote the adherence of tumour cells to the microvasculature by inducing endothelial apoptosis that subsequently induces the expression of various adhesion molecules for tumour cells. This indicates that by tackling the production of ROS preventing tumour recurrence at distant sites might be feasible.