Resistance to Fas-mediated cell death in BeWo and NJG choriocarcinoma cell lines: implications in immune privilege

• Published in: Gynecologic oncology Vol. 91; no. 1; pp. 89 - 100
• Main Authors: Rajashekhar, G, Loganath, A, Roy, A.C, Mongelli, J.M
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.10.2003; Elsevier
• Subjects: Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Apoptosis; Apoptosis - immunology; Biological and medical sciences; Carrier Proteins - biosynthesis; Carrier Proteins - immunology; CASP8 and FADD-Like Apoptosis Regulating Protein; cFLIP; Choriocarcinoma - immunology; Choriocarcinoma - metabolism; Choriocarcinoma - pathology; Coculture Techniques; Cycloheximide; Dose-Response Relationship, Immunologic; Down-Regulation; Fas Ligand Protein; fas Receptor - immunology; FasL; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Humans; Immune privilege; Intracellular Signaling Peptides and Proteins; Jurkat Cells; Medical sciences; Membrane Glycoproteins - immunology; Pregnancy; T-Lymphocytes - immunology; T-Lymphocytes - pathology; Tetrazolium Salts; Thiazoles; Tumor Cells, Cultured; Tumors; Uterine Neoplasms - immunology; Uterine Neoplasms - metabolism; Uterine Neoplasms - pathology; Cycloheximide; Immune privilege; cFLIP; FasL; Apoptosis; Human; Fas ligand; Trophoblaste pathology; Statistical analysis; Pregnancy disorders; Hydatidiform mole; Malignant tumor; Placenta diseases; Secretory tumor; Choriocarcinoma; Resistance; Cell line; Placenta; Cell death; Tumor; Female; Molecular biology; Reverse transcription polymerase chain reaction; Immune system
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/S0090-8258(03)00396-2

An immune privileged site occurs when the allogenic tissue grafts have the propensity for prolonged survival in the host tissue. In this context, the survival and proliferation of malignant trophoblasts in the gravid uterus are currently unclear. In a previous study, we documented that Fas and FasL are coexpressed in choriocarcinoma [Gynecol. Oncol. (2003)]. This study was conducted to examine the role of the Fas/FasL pathway in immune privilege of BeWo and NJG choriocarcinoma cells in culture. The ability of anti-Fas mAb (CH-11) to sensitize choriocarcinoma cell lines to Fas-mediated cytotoxicity was assessed by MTT assays. Coculture experiments with Fas-sensitive Jurkat cells were used to demonstrate functional FasL from choriocarcinoma. RT-PCR was used to assess the expression of cFLIP. The mean cell viability of BeWo and NJG cells declined to about 58 and 63% compared to controls after 72 h of culture in the presence of anti-Fas mAb (CH-11) while the Fas-sensitive Jurkat cells showed viability of only 10%. This resistance to Fas-mediated apoptosis in choriocarcinoma cells is reversed in the presence of cycloheximide (0.5 μg/ml) which further decreased the viability to 36 and 32%, respectively, at a dose of 300 ng/ml ( P < 0.05). The observed resistance to Fas-mediated apoptosis therefore could be attributed to the short-lived endogenous inhibitor, cFLIP as demonstrated by the RT-PCR technique. In coculture experiments, FasL from choriocarcinoma cells induced apoptosis in the Fas-sensitive Jurkat cells, thereby indicating the capacity to evade immune attack. Decreased sensitivity to Fas-mediated apoptosis and counterattacking the lymphocytes may impart immune privilege in these malignant trophoblasts for prolonged survival in the host.