[Tumor escape mechanism involving Fas and Fas-L molecules in human colorectal tumors].
OBJECTIVE
The interaction between Fas and its ligand (Fas-L) leads to Fas-positive cell apoptosis. Our objective was to study a new mechanism of tumor escape involving these molecules, the so-called "counterattack".


METHODS
We used flow cytometry to analyze Fas expression and apoptosis sensitivity in different human colorectal tumor cell lines. The presence of Fas-L mRNA was analyzed by RT-PCR. We studied apoptosis rate in peripheral blood lymphocytes and lymph node lymphocytes from patients with colorectal cancer by flow cytometric cell cycle analysis after in vitro culture with or without tumor cells.


RESULTS
We found differences in Fas expression and sensitivity to Fas-induced apoptosis between different colorectal tumor cell lines. Interferon-gamma was also found to affect Fas expression and apoptosis sensitivity induced by an anti-Fas antibody. Actinomycin-D decreased Fas expression and apoptosis sensitivity in certain cell lines. Our data confirmed the tumor cell "counterattack" hypothesis by showing their capacity to induce apoptosis in lymphocytes from patients with colorectal cancer.


CONCLUSIONS
Fas expression and apoptosis sensitivity in colorectal tumor cell lines can be modulated by actinomycin-D or interferon-gamma. These data may suggest new therapeutic options based on increased Fas expression in tumor cells induced by interferon-gamma, or on apoptosis induction in tumor cells with a local intratumoral treatment with actinomycin-D.
Radfar
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INSERM Unité 395 "Réponse immunitaire et complexe majeur d'histocompatibilité", CHU Purpan, Toulouse, France.
Martin
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Tilkin-Mariame
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D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology*; D003609:Dactinomycin / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000235:genetics* / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology; D019139:Tumor Escape / Q000187:drug effects / Q000235:genetics* / Q000276:immunology*; D019014:fas Receptor / Q000187:drug effects / Q000235:genetics* / Q000276:immunology*
D000970:Antineoplastic Agents; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor; D003609:Dactinomycin; D007371:Interferon-gamma