Role of trace elements in colorectal liver metastases

• Main Author: Gurusamy, K. S.
• Published: University College London (University of London) 2011
• Subjects: 617
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.625557

Trace elements are involved in many key metabolic pathways. Literature review demonstrated that the trace element content in liver metastases is lower than that in surrounding livers and that in livers of normal individuals. The significance of trace elements in the diagnosis, prognosis, and treatment of patients undergoing surgical resection for colorectal liver metastases (CLM) is not known. Samples obtained from patients who underwent liver resection for colorectal liver metastases were used for this research. Iron, copper and zinc content were measured by X-ray fluorescence (XRF) and were confirmed to be lower in colorectal liver metastases than normal liver. Measuring zinc levels in the tissues could differentiate CLM and normal liver with a sensitivity and specificity of 100% and 93.1% respectively. There was a positive correlation between zinc content but not copper content and microvessel density (MVD), a surrogate marker of angiogenesis. However, tumour copper content was found to be a very good predictive factor of survival in patients undergoing liver resection for CLM (area under receiver operating characteristics curve - AUROC 0.919). Micro-XRF revealed that the zinc was preferentially found in normal liver cells (hepatocytes) followed by tumour cells and found least in fibrous stroma. ZnT1, the main zinc efflux transporter, was downregulated in CLM compared with normal liver (5.2 fold, P = 0.002 respectively). Tissue culture experiments using the cell line HT-29 demonstrated no correlation between zinc in culture medium and the main zinc transporters (ZnT1 and ZIP1). However, zinc chelation inhibited genetic markers of apoptosis and angiogenesis and was lethal to the HT-29 cell line. Zinc did not have any effect on cell viability but had a protective effect against short periods of zinc chelation. This thesis has demonstrated unique and biologically important relationships between zinc levels and colorectal metastases which require further biochemical and genetic investigation.