Stimulation of CD40 in human bladder carcinoma cells inhibits anti-Fas/APO-1 (CD95)-induced apoptosis.

CD40 and the CD95 (Fas/APO-1 antigen) are both members of the tumor necrosis factor receptor family. Whereas CD40 mediates a strong growth stimulatory signal in B cells, engagement of the CD95 receptor leads to growth inhibition and induction of apoptosis. As it has been reported that CD40 activation may rescue B cells from undergoing apoptosis, we were interested to see whether it had a similar effect in other cells expressing the CD40 receptor. We used epithelial tumor cells from the urinary bladder, a cell type that frequently expresses CD40 but for which no clear function of the molecule has been assigned. We found that the ligation of CD95 with the antibody anti-APO-1 induced apoptosis in most of the cell lines tested. Stimulation of CD40 with antibodies or a soluble construct of the CD40 ligand was shown to protect cells from apoptosis, as demonstrated by their ability to suppress the growth inhibition exerted by the anti-APO-1 antibody. Our results show that CD40 stimulation make cells less vulnerable to apoptosis induced via CD95 and suggest that CD40 expression on epithelial tumors may be associated with cell survival.