Inverse relationships between cell proliferation and basal or androgen-stimulated apolipoprotein D secretion in LNCaP human prostate cancer cells.

We have recently demonstrated that the biphasic action of androgens on LNCaP cell proliferation is opposite to their effect on apolipoprotein D (apo-D) secretion, the stimulation of apo-D secretion being associated with a steroid-induced inhibition of cell proliferation. To further characterize the control of apo-D expression in LNCaP cells, we studied basal as well as androgen-induced apo-D secretion in slowly proliferating, low-passage (LP; 20-29th) and rapidly proliferating high-passage (HP; 111-117th) cell cultures. For comparison, the androgen-induced stimulation of prostate specific antigen secretion was also investigated in LP and HP cell cultures. In the absence of androgens, basal cell proliferation of HP cells was significantly higher than that of LP cells, whereas apo-D secretion was higher in LP cells than in HP cells. Furthermore, the biphasic action of dihydrotestosterone and of the synthetic androgenic compound R1881 on apo-D release and cell proliferation was observed in both LP and HP cells. The stimulation of apo-D secretion was inversely related to that of cell proliferation and influenced by cell density. The inhibition of basal and androgen-induced cell proliferation by the calcium channel blocker nifedipine was also associated with an increase in apo-D secretion. The amount of PSA released and the sensitivity of its response to R1881 were increased in LP cells compared with HP cells. The present study thus demonstrates, for the first time, that apo-D secretion is inversely correlated to cell proliferation and cell density in the absence as well as in the presence of androgens in both LP and HP LNCaP human prostate cancer cells. This finding suggests that apo-D expression can be modulated not only by steroid hormones, but also by other factors involved in the control of cell proliferation.