Accelerated growth of human colon cancer cells in nude mice undergoing liver regeneration

The purpose of this study was to determine whether liver regeneration induced by partial hepatectomy (PH) influences the growth of human colon cancer (HCC) cells implanted into athymic nude mice. HCC KM12C cells were injected subcutaneously into nude mice and then the mice were randomized to undergo PH, laparotomy, or no surgery. The latent period to development of measurable tumors was shorter and the growth rate of HCC tumors was significantly faster in hepatectomized mice. Accelerated tumor growth directly coincided with liver regeneration. Peak mitotic activity in both the regenerating liver and HCC occurred on the second day following PH. No enhancement in growth of tumors occurred in mice implanted with HCC cells 3 weeks after PH (i.e. 2 weeks after completion of liver regeneration). The accelerated tumor growth was specific to HCC. We base this conclusion on results of control experiments where cells from human melanoma, colon, breast, prostate, and renal cancer were injected into nude mice that were then randomized to undergo PH or laparotomy. Only HCC grew faster in hepatectomized mice. No significant differences in expression of epidermal growth factor receptor (EGF-R) and c-met were found between HCC tumors in mice with PH or laparotomy, suggesting that over-expression of EGF-R or c-met is not an essential component of this phenomenon. The accelerated growth of HCC cells at a site distant from surgical trauma suggests that circulating growth factors involved in liver regeneration can specifically stimulate the growth of HCC cells.