RECOMBINANT HUMAN UTEROGLOBIN INHIBITS THE IN-VITRO INVASIVENESS OF HUMAN METASTATIC PROSTATE TUMOR-CELLS AND THE RELEASE OF ARACHIDONIC-ACID STIMULATED BY FIBROBLAST-CONDITIONED MEDIUM

Uteroglobin (UG) is a potent immunomodulatory and antiinflammatory sec retory protein with high levels detected in human prostate tissue. We used three human prostate cancer cell lines (DU-145, PC3-M, and LNCaP) to test the hypothesis that UG may modulate invasiveness of prostatic carcinoma cells in the Boyden chamber assay for invasion through a re constituted basement membrane preparation. Fibroblast-conditioned medi um was used as the chemoattractant. The most invasive cell line was DU -145, followed by PC3-M, whereas the androgen-dependent LNCaP cell lin e exhibited extremely low invasive potential. Pretreatment of DU-145 a nd PC3-M cells for 24 h with 0.01, 0.1, or 1.0 mu M recombinant UG had no effect on basal invasiveness but inhibited fibroblast-conditioned medium-stimulated invasion in a dose-dependent manner, reaching up to 60.2 and 87.9% inhibition of DU-145 and PC3-M, respectively. UG had no effect on either cell-reconstituted basement membrane adhesion or sim ple chemotaxis in the absence of reconstituted basement membrane. UG a lso strongly inhibited the biphasic release of [C-14]-labeled arachido nic acid from fibroblast-conditioned medium-stimulated DU-145 cells. T hese results suggest that UG may modulate prostate tumor cell invasive ness and that the mechanism may include inhibition of the arachidonic acid signal cascade.