Induction of Fas and Fas ligand expression on malignant glioma cells by Kupffer cells, a potential pathway of antiliver metastases

Kupffer cells play an important role in controlling the growth and developm ent of liver metastases. However, the pathway of Kupffer cells against tumo r metastases is not clear. In the present study, we set up an experimental model to investigate the mechanisms on how Kupffer cells kill tumor cells w hich metastasize to the liver. Malignant glioma cells were cocultured with Kupffer cells or treated with culture medium collected from lipopolysacchar ide (LPS)-activated Kupffer cells. The results showed that the interaction between Kupffer cells and malignant glioma cells significantly stimulated t he generation of tumor necrosis factor alpha (TNF alpha). TNF alpha was mai nly produced by Kupffer cells, as its level in culture medium obtained from LPS-treated Kupffer cells was not significantly different from that of mal ignant glioma cells treated with the same medium. Both Kupffer cells and LP S/Kupffer cell-conditioned supernatants induced expression of Fas and Fas l igand on malignant glioma cells. Subsequently a significant proportion of m alignant glioma cells became apoptotic, as evidenced by positive staining o f annexin V and propidium iodine and an increase in cellular DNA fragmentat ion. Therefore, this study supports a novel pathway of Kupffer cells agains t liver metastases, in which tumor cells were apoptotic via the Fas-Fas lig and system induced by TNFa released from Kupffer cells. (C) 2001 Academic P ress.