Polymorphonuclear leukocytes increase the adhesion of circulating tumor cells to microvascular endothelium

Background: Reactive oxygen species (ROS) released from activated polymorphonuclear leukocytes (PMN) during surgery may play a crucial role in the enhanced distant tumor recurrence after surgical trauma. Materials and Methods: The effect of PMN on the adhesion of the human colon carcinoma cells HT29, Caco2 and the pancreatic carcinoma cells PanC1 and BxPC3 to microvascular endothelium (MEC) was studied in a reproducible human in vitro model. Results: Pre-incubation of MEC with tissue plasminogen activator (TPA)-activated PMN resulted in more than 200% increase of tumor cell adhesion to MEC compared to control (p<0.01). Exposure of MEC to TPA or non-activated PMN did not significantly affect adhesion. Addition of the antioxidant enzymes superoxide dismutase or catalase significantly decreased tumor cell adhesion to MEC exposed to PMN. Conclusion: These results demonstrate that activated PMN promote tumor cell adhesion to the microvascular wall by production of ROS. This indicates that in tackling the ROS production, preventing tumor recurrence at distant sites, might be feasible.