Gastric cancer cell lines lack Fas ligand (FasL) expression but kill T cells via a FasL independent pathway
2000
Editor,—Bennett et al ( Gut 1999; 44 :156–162) reported that in each of 30 paraffin wax specimens of human gastric adenocarcinomas, FasL mRNA and protein co-localised to neoplastic epithelial cells. TUNEL staining revealed that a high number of tumour infiltrating lymphocytes (TIL) displayed apoptotic features. From these results and from their findings of FasL expression in human colon1 and oesophageal cancer,2 the authors propose that FasL might be a mediator of immune privilege in gastrointestinal cancers.
We studied intrinsic FasL expression in gastric cancer cell lines derived from primary (RF-1, SNU-1) or from metastatic sites (SNU-16, Kato-III , N-87, RF-48). We did not detect FasL mRNA or protein in any of the six cell lines analysed by RT-PCR and by flow cytometry (table1).3 4 We then performed the JAM assay to rule out the presence of a functional FasL expression below the detection limit of our assays.5 Although we found that gastric cancer cells were able to induce DNA fragmentation in the Fas sensitive T-acute lymphocytic leukaemia cell line CEM-C7H2 (fig 1A), blocking FasL on the effector cell site did not reduce the extent of cytotoxicity. This result was confirmed by replacing the target cell line by a subclone stably expressing the viral cowpox protein crmA, which inhibits activation of caspases 1 and 8 and thereby mediates resistance to Fas triggering (fig1B).6
View this table:
Table 1
Expression of FasL and Fas in gastric cancer cell lines and their sensitivity toward Fas triggering by the CH11 monoclonal antibody
Figure 1
CEM-C7H2 T-acute lymphocytic leukaemia cells are killed by gastric carcinoma cell lines via a FasL independent pathway. (A) CEM-C7H2 target cells were incubated with 10 μCi/ml [3H]-thymidine for 16 hours and cocultivated with the gastric cancer cell lines at a target:effector ratio of 1:10. …
Professor Shanahan, Department of Medicine, Clinical Sciences Building, University Hospital, Cork, Ireland
Professor Shanahan, Department of Medicine, Clinical Sciences Building, University Hospital, Cork, Ireland
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