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Recombinant Human Uteroglobin Inhibits the in Vitro Invasiveness of Human Metastatic Prostate Tumor Cells and the Release of Arachidonic Acid Stimulated by Fibroblast-conditioned Medium¹

Departments of Pharmacology [J. L., S. R. P.] and Urology [M. J. M.], The George Washington University Medical Center, Washington, DC 20037, and Section on Developmental Genetics, Human Genetics Branch, National Institute of Child Health and Human Development, NIH, Bethesda, Maryland 20892 [A. B. M., L. M., G. M.]

Uteroglobin (UG) is a potent immunomodulatory and antiinflammatory secretory 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 reconstituted basement membrane preparation. Fibroblast-conditioned medium was used as the chemoattractant. The most invasive cell line was DU-145, followed by PC3-M, whereas the androgen-dependent LNCaP cell line exhibited extremely low invasive potential. Pretreatment of DU-145 and PC3-M cells for 24 h with 0.01, 0.1, or 1.0 µM 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 simple chemotaxis in the absence of reconstituted basement membrane. UG also strongly inhibited the biphasic release of [¹⁴C]-labeled arachidonic acid from fibroblast-conditioned medium-stimulated DU-145 cells. These results suggest that UG may modulate prostate tumor cell invasiveness and that the mechanism may include inhibition of the arachidonic acid signal cascade.

¹ Supported by a George Washington University Clinician-Scientist Research Grant.

² Present address: Center for Biologic Research and Evaluation, Laboratory of Cell Biology, FDA, Building 29, Room 225, Bethesda, MD 20892.

³ To whom requests for reprints should be addressed, at Department of Pharmacology, The George Washington University, 2300 I St. NW, Washington, DC 20037.

Received 4/12/94. Accepted 6/ 2/94.

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