Regulation of transforming growth factor-beta secretion by human peritoneal mesothelial and ovarian carcinoma cells

This study was conducted to compare the secretion of TGF-beta isoforms by h uman ovarian carcinoma (OVCA) cell lines (n=12) and human peritoneal mesoth elial cells (HPMC; n=6) and to examine the regulation of their production b y inflammatory cytokines. TGF-beta isoforms mere furthermore analysed in OV CA-associated ascitic fluids. HPMC constitutively produced considerable amo unts of TGF-beta 1 (median 32 pg/10(5) cells; range 7-98) but only minimal amounts of TGF-beta 2 (median 0.8 pg/10(5) cells; range 0-1,5). Treatment o f HPMC with IL-1 beta (10 ng/ml) resulted in a significant elevation of the secretion of both TGF-beta 1 (median 187 pg/10(5) cells; range 71-263; P<0 ,001) and TGF-beta 2 (median 1.8 pg/10(5) cells; range 0-13; P<0,01), In OV CA TGF-beta 1 and TGF-beta 2 were detected in 7/12 and 11/12 of the cell li nes, respectively, The levels detected varied widely for TGF-beta 1 (median 25 pg/10(5) cells; range 0-410) as well as for TGF-beta 2 (median 14 pg/10 (5) cells; range 0-419) and there was no correlation between the two isofor ms, In contrast to HPMC, TGF-beta secretion by OVCA was not affected by any of the inflammatory cytokines tested. TGF-beta 3 could not be detected in supernatants, neither in OVCA nor in HPMC. In ascitic fluids the median lev el of TGF-beta 1 (median 5443 pg/ml; range 737-14687) was 10-fold higher th an the level of TGF-beta 2 (median 545 pg/ml; range 172-3537), The present data provide a model for the analysis of the molecular mechanisms of aberra nt TGF-beta production by OVCA and support the hypothesis that HPMC are an important source of ascitic TGF-beta. (C) 2000 Academic Press.