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Human colon cancer cells express the functional Fas ligand
E X Ding1, A Hizuta, Y Morimoto
1First Department of Surgery, Okayama University Medical School, Japan.
Abstract:
Fas ligand (FasL) belongs to the TNF superfamily. It is induced in activated lymphocytes and eliminates Fas-positive lymphocytes, resulting in the down-regulation of immune responses. FasL has also been detected in tissues other than lymphoid cells. We investigated the expression and function of FasL on human colon cancer cells. FasL mRNA was detected by RT-PCR in all six colon cancer cell lines tested and was not found on fibroblasts. FasL protein was detected in DLD-1, LoVo, HCT-116 and RPMI 4788 cells by immunohistochemical staining. DLD-1, LoVo and WiDr were cytotoxic against mouse T lymphoma cells which were transfected with human Fas receptor cDNA. The cytotoxicity was significantly enhanced by phorbol 12-myristate 13-acetate (PMA) and ionomycin. Our data suggest that the FasL expressed in human colon cancer cells may be regulated by endogenous factors in the microenvironment of the host and facilitates the escape from the host immune system.
Insights
Human colon cancer cells express Fas ligand (FasL), a protein that helps them evade the immune system. This FasL expression may be influenced by the tumor microenvironment, aiding cancer cell survival.
Area of Science:
- Immunology
- Oncology
Background:
- Fas ligand (FasL) is a key mediator in immune response regulation, primarily expressed by activated lymphocytes to eliminate Fas-positive cells.
- While known for its role in lymphoid tissues, FasL expression has also been observed in non-lymphoid cells, suggesting broader functions.
Purpose of the Study:
- To investigate the expression and functional role of Fas ligand (FasL) in human colon cancer cells.
- To determine if colon cancer cells utilize FasL to interact with the host immune system.
Main Methods:
- Reverse Transcription Polymerase Chain Reaction (RT-PCR) was used to detect FasL mRNA in colon cancer cell lines and fibroblasts.
- Immunohistochemical staining was employed to identify FasL protein expression in specific colon cancer cell lines.
- Cytotoxicity assays were performed using mouse T lymphoma cells transfected with human Fas receptor cDNA to assess the functional activity of cancer cell-expressed FasL.
Main Results:
- FasL mRNA was ubiquitously detected in all six human colon cancer cell lines tested, but not in fibroblasts.
- FasL protein was confirmed in DLD-1, LoVo, HCT-116, and RPMI 4788 colon cancer cell lines.
- Colon cancer cell lines (DLD-1, LoVo, WiDr) exhibited cytotoxicity against Fas receptor-expressing T lymphoma cells, with enhanced effects upon stimulation with PMA and ionomycin.
Conclusions:
- Human colon cancer cells express functional FasL, indicating a potential mechanism for immune evasion.
- The expression and activity of FasL on colon cancer cells may be modulated by factors within the host's tumor microenvironment.
- FasL expressed by colon cancer cells could contribute to the tumor's ability to escape host immune surveillance and destruction.