CD40 stimulation inhibits cell growth and Fas-mediated apoptosis in a thyroid cancer cell line.
CD40 plays a critical role in the humoral immune response, especially in B-cell proliferation, differentiation, production of antibody, secretion of cytokines, and apoptosis. Here, we examined CD40 expression on six head and neck cancer cell lines by flow cytometry. Only the HTC/C3 cell line, which originated from a thyroid cancer, expressed CD40 on the surface of the cells. Coculture with anti-CD40 mAb inhibited colony formation of HTC/C3 cells. CD40 stimulation enhanced Fas expression on HTC/C3 cells. Although HTC/C3 cells are sensitive to Fas-mediated apoptosis, CD40 stimulation inhibited Fas-mediated apoptosis in HTC/C3 cells. CD40 stimulation enhanced Bcl-2 expression, and antisense oligonucleotide against bcl-2 canceled the inhibition of HTC/C3 cell growth caused by CD40 stimulation. Additionally, more anti-CD40 mAb-treated HTC/C3 cells were accumulated in G1 phase, and fewer in S phase, compared to nontreated cells. These results suggest that CD40 stimulation might be involved in the slow growth rate of CD40-bearing cancer cells, and they suggest a new biological approach to the treatment of cancers.
Fujieda
S
S
Department of Otorhinolaryngology, Fukui Medical University, Yoshida, Japan. sfujieda@fmsrsa.fukui-med.ac.jp
Sugimoto
C
C
Seki
M
M
Sunaga
H
H
Saito
H
H
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D019013:CD40 Antigens / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D016193:G1 Phase / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013964:Thyroid Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014410:Tumor Stem Cell Assay; D019014:fas Receptor / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor