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 c ytokines, 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 cell s. 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 F as-mediated apoptosis in HTC/C3 cells. CD40 stimulation enhanced Bcl-2 expr ession, 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 G(1) phase, and fewer in S phase, compared to nontreated cells. These results suggest that CD40 stim ulation might be involved in the slow growth rate of CD40-bearing cancer ce lls, and they suggest a new biological approach to the treatment of cancers .