8:40 AM Abstract No. 190 - Sublethal thermal stress induces accelerated proliferation and growth factor expression in hepatocellular carcinoma

Abstract

Purpose Tumor recurrence following percutaneous thermal ablation of hepatocellular carcinoma (HCC) remains a significant clinical problem, particularly in tumors ≥3.0cm. The aim of the present study was to test the hypothesis that sublethal heat stress of HCC cells or hepatocytes stimulates accelerated proliferation of non-heat stressed HCC cells and to identify candidate heat-stress induced pro-tumorigenic growth factors. Materials and Methods A small number of HCC cells stably transfected to constitutively express firefly luciferase (N1S1luc and AS30Dluc) were co-cultured with a feeder layer of non-transfected HCC cells (N1S1 or AS30D) or hepatocytes (Clone9) that were heat stressed to induce complete (50 C), partial (45 C) or no (37 C) cell death (N=3). Proliferation of non-heat stressed HCC cells was monitored by non-invasive molecular bioluminescence imaging from 0-6 days using IVIS 200 and a standard curve was generated to estimate cell number in vitro. The two HCC cell lines and the hepatocyte cell line underwent sublethal heat stress (45 C) or control (37 C) and recovered after 6 hours at 37 C for whole transcriptome microarray analysis to assess heat stress induced growth factor expression (N=4). Results Sublethal heat stress (45 C) of both HCC cells and hepatocytes induced a significant increase in proliferation of non-heat stressed N1S1luc (p Conclusion These data suggest that sublethal thermal injury to HCC cells and hepatocytes stimulates proliferation of residual HCC cells and induces a significant increase in numerous pro-tumorigenic growth factors. Thermal ablation induced growth factor signaling warrants further investigation as a mechanism for recurrence and progression following thermal ablation of HCC.