Changes in growth factor levels after thermal ablation in a murine model of colorectal liver metastases

Objectives: This study examines changes in the expression of growth factors following thermal ablation (TA) of selected colorectal cancer (CRC) liver metastases. Methods: Using mice with established CRC liver metastases, two tumours in each animal were thermally ablated. Liver and tumour tissues were collected at various time-points (days 0, 1, 2, 3, 5 and 7) following TA treatment from the ablation site and from sites distant from ablated tumour. Changes in growth factor expression (epidermal growth factor [EGF], vascular endothelial growth factor [VEGF], hepatocyte growth factor [HGF] and transforming growth factor-beta [TGF-beta]) in comparison with baseline levels (non-ablated) were assessed by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. Results: Baseline TGF-beta and VEGF levels in the liver parenchyma of tumour-bearing mice were significantly higher than levels in naive liver parenchyma. Levels of VEGF and HGF decreased after TA treatment in all tissues. Levels of EGF decreased in ablated and distant tumour tissues, but displayed a tendency to increase in liver tissue. Levels of TGF-beta also decreased during the first 2 days following TA, but later increased in liver and tumour tissues distant from the ablation site to a level that reached significance in tumour tissue at day 7 (P < 0.001). Decreases in growth factor levels were also observed in animals that underwent laparotomy without TA treatment, which indicates that these decreases were caused by the experimental procedure. Conclusions: Tumour induces upregulation of TGF-beta and VEGF in liver parenchyma. Growth factors decreased after TA, but this appears to be the result of the experimental procedure rather than the TA itself. However, TA resulted in increased levels of TGF-beta, which may contribute to tumour recurrence.