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

Abstract

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, Po0.01), Caco2 (164% vs control, Po0.01) and of the pancreas carcinoma cells PanC1 (180% vs control, Po0.01). Addition of the antioxidant enzymes superoxide dismutase or catalase significantly decreased tumour cell adhesion (Po0.01). 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 (Po0.01). 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.

Endothelial NO synthase and reactive oxygen species mediated effect of simvastatin on vessel structure and function: Pleiotropic and dose-dependent effect on tumor vascular stabilization

“…In addition, elevated ROS was shown to trigger ECs apoptosis that resulted in the loss of vascular barrier integrity. Application of anti-oxidants may abrogate the ROS-induced impairment of endothelial barrier (16,49). These data are intriguing and together implicate the critical role of endogenous ROS in abnormalities of tumor vessel structure and functions.…”

High expression of GCLC is associated with malignant melanoma of low oxidative phenotype and predicts a better prognosis

“…One of the major adhesion molecules mediating these processes is ICAM-1. It has been shown that ROS and antioxidants affect its expression in an opposed way resulting in substantial consequences for the disease course [32,33]. During tumorigenic transition in melanoma, loss of E-cadherin is accompanied by gain in N-cadherin.…”

Less stress, more success? Oncological implications of surgery-induced oxidative stress

“…There is growing evidence that surgical trauma induces ROS which have oncological implications that can facilitate tumour growth and metastasis 3 9 10. Both clinical and animal studies have shown that the trauma response associated with a laparotomy is responsible for a significant rise in ROS levels 9 59–61.…”

“…Consequently, surgical trauma creates an ROS-rich environment which allows redox signalling to occur 9 10. Emerging evidence clearly demonstrates that surgery-induced ROS is a key player in the development of local recurrence and distant metastasis following tumour resection 3 11 12.…”