Requirement of cyclooxygenase-2 expression and prostaglandins for human prostate cancer cell invasion

The PC-3 Low Invasive cells and the PC-3 High Invasive cells were used to investigate the correlation of the COX-2 expression and its arachidonic acid metabolites, prostaglandins, with their invasiveness through Matrigel(R) using a Boyden chamber assay. The COX-2 expression in PC-3 High Invasive cells was approximately 3-fold higher than in PC-3 Low Invasive cells while the COX-1 expression was similar in both cell sublines. When incubated with arachidonic acid, PGE(2) was the major prostaglandin produced by these cells. PC-3 High Invasive cells produced PGE(2) approximately 2.5-fold higher than PC-3 Low Invasive cells. PGD(2) was the second most abundant prostaglandin produced by these cells. Both indomethacin (a nonspecific COX inhibitor) and NS-398 (a specific COX-2 inhibitor) inhibited the production of prostaglandins and the cell invasion. PGE(2) alone did not induce the cell invasion of PC-3 Low Invasive cells. However, PGE(2) reversed the inhibition of cell invasion by NS-398 and enhanced the cell invasion of the PC-3 High Invasive cells. In contrast, PGD(2) slightly inhibited the cell invasion. These results suggest that in the PC-3 Low Invasive cells, COX-2-derived PGE(2) may not be sufficient to induce cell invasion while in the PC-3 High Invasive cells, PGE(2) may be sufficient to act as an enhancer for the cell invasion. Further, PGD(2) may represent a weak inhibitor and counteracts the effect of PGE(2) in the cell invasion.