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. 2001 May;84(9):1265–1271. doi: 10.1054/bjoc.2000.1737

Kupffer cells of cirrhotic rat livers sensitize colon cancer cells to Fas-mediated apoptosis

E Song 1,3, J Chen 3, N Ouyang 1, M Wang 1,3, M S Exton 1,2, U Heemann 1
PMCID: PMC2363876  PMID: 11336480

Abstract

Metastasis of colorectal carcinomas rarely occurs in cirrhotic livers. Our study investigated the influence of activated Kupffer cells from cirrhotic rat livers on hepatic colonization and FasR-mediated apoptosis of colon cancer cells. A rat colon cancer cell line, RCN-9, was used to inoculate rat livers. Treatment with conditioned media of Kupffer cells isolated from CCl 4-induced cirrhotic rat livers (cirrhotic KCM) significantly reduced the incidence of hepatic colonization of RCN-9 cells. In vitro cytotoxicity of Kupffer cells and tumour infiltrating lymphocytes (TILs) on RCN-9 cells was evaluated using [3H]-release assay. RCN-9 cells were resistant to cytotoxicity mediated by cirrhotic Kupffer cells, but were sensitized to TIL-mediated killing after treatment with cirrhotic KCM. The specific killing induced by TILs was FasR-mediated, as it was inhibited by ZB4, an antagonistic anti-FasR antibody. In agreement, cirrhotic KCM increased recombinant Fas ligand-induced apoptosis of RCN-9 cells, and up-regulated FasR expression on RCN-9 cells as evaluated by RT-PCR and flow cytometry. These findings suggest that Kupffer cells in cirrhotic livers sensitize metastatic colon cancer cells to FasR-mediated apoptosis by up-regulating the receptors, which thus prepare them to be eliminated by infiltrating lymphocytes. © 2001 Cancer Research Campaign http://www.bjcancer.com

Keywords: colon neoplasms, metastasis, liver cirrhosis, Kupffer cells, apoptosis

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Selected References

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