Radiation-induced expression of functional Fas ligand in EBV-positive human nasopharyngeal carcinoma cells.
Ionizing radiation remains a major therapeutic tool against human cancers, especially epithelial tumors, which account for the majority of human malignancies. Although Fas and Fas-L are essential determinants of apoptosis, few data support their role in the cytotoxic effect of ionizing radiation. Epstein-Barr-virus (EBV)-positive nasopharyngeal carcinoma (NPC) were chosen to address this question owing to their known sensitivity to ionizing radiation and their constitutive expression of the Fas-receptor. We here report that, in xenografted NPC cells, Fas-L expression, which was very low in basal conditions, was dramatically increased by tumor irradiation. Both the Fas receptor and the Fas ligand were found to be functional in this model, and a high proportion of irradiated NPC cells underwent apoptosis following tumor irradiation. Induction of Fas-L expression and apoptosis were observed for doses as low as 2 Gy. These data show an increase in Fas-L expression upon irradiation exposure, and strongly suggest that, in some epithelial malignancies, Fas-mediated apoptosis can play a major role in the anti-tumor effect of ionizing radiation, in the range of doses used for therapeutic applications.
Abdulkarim
B
B
UPRES EA 27-10 "Radiosensibilité-Radiocarcinogenèse Humaine" & METSI, Institut Gustave Roussy, Villejuif, France.
Sabri
S
S
Deutsch
E
E
Vaganay
S
S
Marangoni
E
E
Vainchenker
W
W
Bongrand
P
P
Busson
P
P
Bourhis
J
J
D000818:Animals; D017209:Apoptosis; D002462:Cell Membrane / Q000737:chemistry; D004307:Dose-Response Relationship, Radiation; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D019169:Jurkat Cells / Q000473:pathology; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000032:analysis / Q000096:biosynthesis*; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000532:radiotherapy* / Q000821:virology; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous; D019014:fas Receptor / Q000032:analysis / Q000096:biosynthesis*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor