Three-dimensional spheroid cultures of human prostate cancer cell lines

BACKGROUND. Many of the available human prostate cancer (PC) cell lines hav e lost androgen sensitivity and no longer secrete prostate-specific protein s after serial culturing in cell monolayers. Three-dimensional spheroid cul tures have been found to better mimic the in vivo phenotypes of several non prostatic cell lines. METHODS. We analyzed seven PC cell lines to determine if spheroid culturing results in greater sensitivity to androgens and 1 alpha,25(OH)(2) vitamin D-3 (1,25(OH)(2) D-3) with regards to their growth, differentiation, and ap optotic potential. RESULTS. Only PC-3 cells showed greater sensitivity to the growth-inhibitor y effects of 1,25(OH)(2) D-3, while ALVA-31 showed a diminished response. T he regulation of prostate-specific antigen and prostate-specific acid phosp hatase remained unchanged. However, these studies provided several unique f indings not observed in cell monolayers. First, three basic spheroid morpho logies were observed with varying degrees of intercellular adhesions. Secon dly, the cell lines that formed the tightest spheroids consistently grew at the slowest rates, regardless of their growth rate in monolayers. Lastly, 1,25(OH)(2) D-3 treatment of ALVA-31 and PPC-1 spheroids greatly reduced in tercellular adhesions, and rendered ALVA-31 spheroids resistant to apoptoti c induction by Fas ligand expressed via a recombinant adenoviral construct. CONCLUSIONS. Our results suggest that spheroid cultures of human PC cells m ay provide unique insights regarding cell adhesion and apoptotic potential that are diminished or absent in monolayer cultures. (C) 1999 Wiley-Liss, I nc.