Control of apoptosis in Epstein Barr virus-positive nasopharyngeal carcinoma cells: opposite effects of CD95 and CD40 stimulation.
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.
Sbih-Lammali
F
F
Laboratoire de Biologie des Tumeurs Humaines, UMR 1598 Centre National de la Recherche Scientifique, Institut Gustave Roussy, Villejuif, France.
Clausse
B
B
Ardila-Osorio
H
H
Guerry
R
R
Talbot
M
M
Havouis
S
S
Ferradini
L
L
Bosq
J
J
Tursz
T
T
Busson
P
P
D000293:Adolescent; D017209:Apoptosis; D019013:CD40 Antigens / Q000032:analysis / Q000502:physiology*; D002470:Cell Survival; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000473:pathology* / Q000821:virology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein; D019014:fas Receptor / Q000032:analysis / Q000502:physiology*
C494811:BCL2L1 protein, human; D019013:CD40 Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D019014:fas Receptor