Hyperproliferation of human colon cancer cells in co-cultures of rat regenerating hepatocytes / 国际外科学杂志

ABSTRACT

Objective To investigate the stimulated proliferation of colon cancer cells in co-cultures of regenerating hepatocytes. Methods Regenerating hepatocytes(24 hours after partial hepatectomy)were obtained by collagenase perfusion of models of rats undergoing 70% liver resection. To determine whether the ratio of human colon cell line SW480 cells to hepatocytes in co-cultures has influence on their interaction,these cells were cultured in ratios of 1 1011, or 10 1. Proliferation capacity was assessed by the percentage of 3 H-TdR incorporation. Expression of epidermal growth factor receptor(EGFR), insulin-like growth factor1 receptor(IGF-1R)and hepatocyte growth factor receptor(c-met) were analyzed by western blot. Results For co-cultured SW480 and hepatocytes in the ratios of 1 1 and 1 10, an increase of disintegrations per minute(dpm) occurred after 72 hours' culture, and lasted at 120 hours' culture(P < 0.05). No difference was found between the group with ratio of 101 and control group. Protein levels of EGFR and IGF-1R, but not c-met, were significantly increased between culture of 24 hours and 120 hours; however, no change of these receptors was found in the ratio of 10 1. Conclusions These results imply that co-culturing human colon cancer cells with regenerating hepatocytes leads to increased expression of EGFR and IGF-1R. We conclude that this effect is probably dependent on paracrine stimulation, by which numerous signals from the hepatocytes contribute to the hyperproliferative state of colon cancer cells via up-regulating the responding receptors.