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 col on cancer (HCC) cells implanted into athymic nude mice. HCC KM12C cell s were injected subcutaneously into nude mice and then the mice were r andomized 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. Accelerat ed tumor growth directly coincided with liver regeneration. Peak mitot ic activity in both the regenerating liver and HCC occurred on the sec ond day following PH. No enhancement in growth of tumors occurred in m ice implanted with HCC cells 3 weeks after PH (i.e. 2 weeks after comp letion of liver regeneration). The accelerated tumor growth was specif ic to HCC. We base this conclusion on results of control experiments w here cells from human melanoma, colon, breast, prostate, and renal can cer were injected into nude mice that were then randomized to undergo PH or laparotomy. Only HCC grew faster in hepatectomized mice. No sign ificant differences in expression of epidermal growth factor receptor (EGF-R) and c-met were found between HCC tumors in mice with PH or lap arotomy, suggesting that overexpression of EGF-R or c-met is not an es sential component of this phenomenon. The accelerated growth of HCC ce lls at a site distant from surgical trauma suggests that circulating g rowth factors involved in liver regeneration can specifically stimulat e the growth of HCC cells.