Figure 3.

Mouse hepatocytes subject to hyperthermic doses observed in peri-ablational tissue promote tumor cell growth by producing multiple pro-tumorigenic factors. (A) Purified primary mouse hepatocytes were subjected to moderate hyperthermia doses 45 °C for 5 or 10 min following 1.5–8 h incubation at 37 °C (n = 12). Medium and cells were collected for further analysis. (B) Moderate hyperthermia dose 45 °C × 10 min induces time dependent elevation of HSP70, IL-6, STAT3 and HGF gene expression of mouse primary hepatocytes with maximum expression of each cytokine observed at different incubation times (n = 4, Total = 12). (C) Western blot analysis demonstrates increase P-STAT3 and C-met in the heated mouse hepatocytes (n = 3 each arm, Total N = 9). (D) Medium derived from primary mouse hepatocytes heated to 45 °C × 5 min followed by incubation for 3 h at 37 °C led to significant increased cellular growth for three unheated cancer cell lines (n = 3, Total N = 18). (E) Likewise, multiple growth factors are present in the plasma of mice treated with a single 70 °C × 5 min application of RFA to normal liver, a dose that subjects the peri-ablational rim of hepatocytes to hyperthermic temperature (N = 24). For all experiments p-values calculated by two tailed t-test *p < 0.05, **p < 0.01.