| Fas ligand (FasL) belongs to the tumor necrosis factor family and has the ability to induce apoptosis in susceptible target cells by binding to its receptor, Fas. It has been demonstrated recently that the Fas/FasL system plays a pivotal role in the cytocidal activity of T lymphocytes in the immune system. FasL may act as a cytotoxic effector molecule to Fas - expressing malignant tumor cells.A recent report described the expression of Fas ligand (FasL) by melanoma cells as an important mechanism involved in the immune e-vasion by tumors. To investigate the expression of FasL by melanomas , some scientists used conditions designed to replicate those in the original report. But they did not find functional FasL on any ojf the 19 human melanoma lines established. Furthermore, they additionally e-valuated their melanoma lines using reverse transcriptase - PCR and found that 0 of 26 human melanoma cell lines expressed FasL mRNA. FasL mRNA was abundantly expressed by antimelanoma T cell lines after activation. These data do not support a role for FasL expression in the escape of melanoma cells from immune destruction.Activated T - lymphocytes secrete FasL and kill the tumor cells by engagement of Fas and FasL which can induce apoptosis of tumor cells. FasL over expressed on tumor cells can engage Fas on the surface of lymphocytes and induce apoptosis of T cells. It's common that few T lymphocytes invase in the tumor tissues. Therefore, we suspect that tumor cells have FasL overexpressedon the endotheliums which inhabit the immigration to the tumor tissue of T - lymphocytes.MethodsHendrik etc. have shown that all human pancreatic adenocarcino-ma cell lines tested by fluorescence - activated cell sorting analysis (6 of 6) and immunocytochemistry (12 of 12) were positive for Fas expression. However, despite Fas expression, pancreatic tumor cells have become largely resistant toward recombinant FasL or anti - Apo- 1 agonistic antibody - induced apoptosis. This resistance correlated with high levels in pancreatic tumor cells of mRNA for FAP -1, a Fas?associated phosphatase that can block the apoptotic of Fas. Using a varietyof methodological approaches, they also present evidence for the production of FasL by pancreatic tumor cells because 6of 6 pancreatic tumor cell lines were found to contain FasL mRNA as well as the Mr40,000 and Mr26,000 forms of FasL protein. Likewise, pancreatic tissue revealed FasL - specific immunostaining in pancreatic tumor cells but not in the surrounding stroma. In coculture experiments, pancreatic tumor cells displayed a cytotoxic effect toward the Fas -sensitive Jurkat T - cell line, which could be inhibited by a FasL -specific neutralizing antibody. Together, these results support the recently proposed " counterattack model" for local deletion of tumor -reactive T - cells by tumor cell - derived FasL.H. Udo Kontny etc. have studied the presence and functional ststus of Fas and FasL in Swing's sarcoma. All Ewing' s sarcoma cell lines tested expressed Fas on their surface. Three of the cell lines were readily killed after ligation of the Fas receptor. Four additional cell lines exhibited Fas - mediated apoptosis after preincubation with IFN -r and/or cycloheximide, whereas two cell lines examined were positive for protein by immunoblot, and specificity was confirmed byreverse transcription -PCR. However, using flow cytometric analysis, FasL could only be deteced in Ewings sarcoma cells after permeabili-zation. Furthermore, the cell lines were not capable of including ap-optosis of Fas - sentsitive Jurkat cells. In addition, Ewing's sarcoma cell lines were able to serve as stimulators for the generation of cyto-toxic effector lymphocytes and were susceptible to lysis by them. Therefore, FasL is expressed in Ewings sarcoma but is not functional, suggesting that Ewings sarcoma is a potential target for immunothera-py-In the original research of FasL expressed location, we adopted single immunocytochemistry. This method could not demonstrate whether the ove... |
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