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 human ovarian carcinoma (OVCA) cell lines (n=12) and human peritoneal mesothelial cells (HPMC;n=6) and to examine the regulation of their production by inflammatory cytokines. TGF-beta isoforms were furthermore analysed in OVCA-associated ascitic fluids. HPMC constitutively produced considerable amounts of TGF-beta1 (median 42 pg/10(5)cells; range 7-98) but only minimal amounts of TGF-beta2 (median 0.8 pg/10(5)cells; range 0-1.5). Treatment of HPMC with IL-1beta (10 ng/ml) resulted in a significant elevation of the secretion of both TGF-beta1 (median 187 pg/10(5)cells; range 71-264;P<0.001) and TGF-beta2 (median 1.8 pg/10(5)cells; range 0-13;P<0.01). In OVCA TGF-beta1 and TGF-beta2 were detected in 7/12 and 11/12 of the cell lines, respectively. The levels detected varied widely for TGF-beta1 (median 25 pg/10(5)cells; range 0-410) as well as for TGF-beta2 (median 14 pg/10(5)cells; range 0-419) and there was no correlation between the two isoforms. In contrast to HPMC, TGF-beta secretion by OVCA was not affected by any of the inflammatory cytokines tested. TGF-beta3 could not be detected in supernatants, neither in OVCA nor in HPMC. In ascitic fluids the median level of TGF-beta1 (median 5443 pg/ml; range 737-14687) was 10-fold higher than the level of TGF-beta2 (median 545 pg/ml; range 172-3537). The present data provide a model for the analysis of the molecular mechanisms of aberrant TGF-beta production by OVCA and support the hypothesis that HPMC are an important source of ascitic TGF-beta.