Control of apoptosis in Epstein Barr virus-positive nasopharyngeal carcinoma cells : Opposite effects of CD95 and CD40 stimulation

• Published in: Cancer research (Chicago, Ill.) Vol. 59; no. 4; pp. 924 - 930
• Main Authors: SBIH-LAMMALI, F, CLAUSSE, B, ARDILA-OSORIO, H, GUERRY, R, TALBOT, M, HAVOUIS, S, FERRADINI, L, BOSQ, J, TURSZ, T, BUSSON, P
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.02.1999
• Subjects: Adolescent; Apoptosis; bcl-X Protein; Biological and medical sciences; CD40 Antigens - analysis; CD40 Antigens - physiology; Cell Survival; Epstein-Barr virus; fas Receptor - analysis; fas Receptor - physiology; Female; Herpesvirus 4, Human - isolation & purification; Humans; Medical sciences; Nasopharyngeal Neoplasms - pathology; Nasopharyngeal Neoplasms - virology; Otorhinolaryngology. Stomatology; Proto-Oncogene Proteins c-bcl-2 - analysis; Tumor Cells, Cultured; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Gammaherpesvirinae; Human; Carcinoma; Ligand; Gene product; Herpesviridae; Tumoral tissue; Nasopharynx; Epstein Barr virus; Malignant tumor; Gene expression; In vitro; Biological activity; Virus; Established cell line; ENT disease; Pharynx disease; Tumor cell; Apoptosis
• ISSN: 0008-5472; 1538-7445

The expression and function of CD95 and CD40 were investigated in malignant cells from EBV-positive undifferentiated nasopharyngeal carcinomas (NPCs). Large amounts of CD95 and CD40 expression were detected in 15 of 16 EBV-positive NPC specimens. In contrast, CD95 was not detected in two biopsies from patients with EBV-negative differentiated NPCs. We tested whether the CD95 apoptotic pathway was functional in NPC cells by treating two EBV-positive NPC tumor lines in vitro with a CD95 agonist. In both cases, NPC cells were extremely susceptible to CD95-mediated apoptosis, despite strong constitutive expression of Bcl-x. Combined CD40 and CD95 stimulation was used to investigate the possible anti-apoptotic activity mediated by CD40. The CD40 receptor was activated by incubating NPC cells with murine L cells producing CD154, the CD40 ligand. This treatment resulted in a strong inhibition of CD95-related cytotoxicity. Such an anti-apoptotic effect of CD40 is well known for B lymphocytes, but has not previously been reported for epithelial cells. These data suggest that NPC tumor-infiltrating lymphocytes, which often produce the CD40 ligand in situ, may increase the survival of malignant cells, thereby enhancing tumor growth in patients.