CC531s colon carcinoma cells induce apoptosis in rat hepatic endothelial cells by the Fas/FasL-mediated pathway

The mechanisms involved in colorectal carcinoma with liver metastasis are not well known. Metastasizing colon carcinoma cells express more FasL than primary colon carcinoma cells and cancer cells induce apoptosis in hepatocytes by the Fas/FasL pathway. Therefore, this study focused on Fas/FasL expression and functionality in rat liver sinusoidal endothelial cells (LSECs) and CC531s colon carcinoma cells in vitro and in vivo . RT-PCR and immunochemistry revealed Fas and FasL in LSECs and CC531s, respectively. Functionality of Fas was assessed in vitro by incubation with human recombinant FasL (1-100 ng/ml) with or without enhancer. At concentrations of 10 and 100 ng/ml with enhancer, respectively 21% and 44% of endothelial cells showed signs of apoptosis using Hoechst 33342/propidium iodide staining and electron microscopy. In co-cultures, apoptosis could be detected in endothelial cells neighboring the CC531s and could be inhibited by an antagonistic FasL antibody. Moreover, 18 h after mesenteric injection of CC531s, the sinusoidal endothelium revealed disruption. In conclusion, (i) CC531s cells induce apoptosis in LSECs in vitro by using Fas/FasL; (ii) CC531s cells damage the sinusoidal endothelial lining in vivo ; and (iii) this might provide FasL-positive tumor cells a gateway towards the hepatocytes.