Surgery-induced reactive oxygen species enhance colon carcinoma cell binding by disrupting the liver endothelial cell lining

• DOI: 10.1136/gut.2010.224717
• Publication Date: 2011-01-29T01:41:27Z
• Authors: N. Gul; M. Bogels; S. Grewal; A. J. van der Meer; L. B. Rojas; D. M. Fluitsma; M. P. van den Tol; K. A. Hoeben; J. van Marle; H. E. de Vries; R. H. J. Beelen; M. van Egmond
• Keywords: Male; Biopsy; Macrophages; Carcinoma; Liver Neoplasms; 610; Rats, Inbred Strains; Neoplasms, Experimental; Rats; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Liver; Microscopy, Fluorescence; Cell Line, Tumor; Disease Progression; Microscopy, Electron, Scanning; Animals; Humans; Colorectal Neoplasms; Reactive Oxygen Species; Colectomy; Cell Aggregation

<h3>Objective</h3> Resection of primary colorectal cancer is associated with enhanced risk development liver metastases. It was previously demonstrated that surgery initiated an early inflammatory response resulting in elevated tumour cell adhesion the liver. Because reactive oxygen species (ROS) are shown to be produced and released during surgery, effects ROS on vascular lining were investigated. <h3>Methods</h3> Human endothelial monolayers (human umbilical vein cells (HUVECs) human microvascular lung (HMEC-1s)) exposed production, after which electrical impedance, cellular integrity Furthermore, surgery-induced as well role macrophages (Kupffer cells) this process studied vivo. <h3>Results</h3> Production decreased impedance dramatically. Moreover, formation intercellular gaps observed, exposing subendothelial extracellular matrix (ECM) colon carcinoma adhered via integrin molecules. Endothelial damage was, however, prevented presence ROS-scavenging enzymes. Additionally, induced downregulation both rat tight junction Treatment rats scavenger edaravone proteins Interestingly, depletion Kupffer prior significantly reduced numbers disruption expression proteins. <h3>Conclusions</h3> In study it production by damages downregulating This leads exposure ECM, circulating bind. light this, perioperative therapeutic intervention, preventing reactions, may reduce developing metastases, thereby improving clinical outcome patients cancer.