ORIGINAL ARTICLE: PDF OnlyEffect of retinoic acid on plasminogen activator expression in human melanoma cellsAlexander, C. L.; Edward, M.; MacKie, R. M.Author Information Department of Dermatology, The Robertson Building, University of Glasgow, Glasgow G12 8QQ, UK. Melanoma Research: August 1999 - Volume 9 - Issue 4 - p 360-368 Buy Abstract The plasminogen activation system comprises various proteases that contribute to the invasive potential and metastatic spread of the tumour cell. Two such proteases are tissue-type (tPA) and urokinase-type (uPA) plasminogen activators. Both these enzymes convert plasminogen into the active zymogen plasmin, which has a broad substrate specificity and is capable of degrading a wide range of extracellular matrix molecules. In this study, we examined the effect of retinoic acid (RA) on uPA and tPA secretion in the highly metastatic C8161 and the poorly metastatic Hs294T human melanoma cell lines using a specific enzyme-linked immunosorbent assay (ELISA) detection system, and correlated this production with RA receptor (RAR) expression. Over a range of dilutions, we were able to show that the highly metastatic C8161 cells secreted 0.95 ng of uPA/cell compared with 4.41 fg/cell for the Hs294T cells, whereas the Hs294T cells secreted 24.5 fg of tPA/cell compared with 4.35 fg/cell for the C8161 cells. On exposure of the cells to RA (10-10-10-5 M) for 4 days, uPA secretion was increased 3.4-fold In the C8161 cell line and 1.6-fold in the Hs294T cell line using 10-8MRA. In addition, tPA expression was increased in both cell lines by 3.7-fold in the C8161 cells and 3.8-fold in the Hs294T cells with 10-6 MRA treatment. Increases in PA expression by RA have been reported to involve RARα and RARβ expression. We were able to detect RARβ and γ expression in both cell lines, with and without RA treatment, but were unable to detect expression of RARα. This suggests that another mechanism must exist to regulate the RA modulation of tPA and uPA secretion in these cell lines that does not require RARα expression. © 1999 Lippincott Williams & Wilkins, Inc.