[Interactions of ovarian carcinoma cells and human peritoneal mesothelial cells involved in matrix metalloproteinases expressions of ovarian carcinoma cells].

OBJECTIVE: To investigate the interactions of ovarian carcinoma cells and human peritoneal mesothelial cells (HPMC) involved in matrix metalloproteinases (MMP) expressions of ovarian carcinoma cells.

METHODS: The conditioned medium (CM) of ovarian carcinoma cell SKOV3 was tested by enzyme-linked immunosorbent assay (ELISA) for transforming growth factor beta1 (TGF-beta1). The impact of SKOV3-CM in the presence or absence of TGF-beta1 neutralizing antibody on fibronectin (Fn) gene expression of HPMC was studied by RT-PCR. HPMC were pretreated with serum-free medium, SKOV3-CM, SKOV3-CM + TGF-beta1 neutralizing antibody, and SKOV3-CM + IgG, then the supernatant was collected as HPMC-CM(1), HPMC-CM(2), HPMC-CM(3) and HPMC-CM(4). SKOV3 were incubated with different HPMC-CM, HPMC-CM(1) + antibody against Fn or HPMC-CM(1) + IgG. MMP-2 and MMP-9 gene mRNA expressions and protein expressions of SKOV3 were detected by RT-PCR and ELISA respectively.

RESULTS: TGF-beta1 in SKOV3-CM was (236 +/- 22) ng/L. Fn gene mRNA expressions of HPMC before and after stimulation by SKOV3-CM were 1.328 +/- 0.025 and 2.643 +/- 0.051, and the latter was higher than the former (P < 0.05). Fn gene mRNA expressions of HPMC stimulated by SKOV3-CM + TGF-beta1 neutralizing antibody was 1.897 +/- 0.035, which was less than that of SKOV3-CM group (P < 0.01). Before SKOV3 were incubated with HPMC-CM, MMP-9 protein and mRNA expressions were (14.5 +/- 1.6) microg/L and 1.50 +/- 0.04, but protein and mRNA expressions of MMP-2 were scarcely detected. When SKOV3 were incubated with HPMC-CM(1), mRNA expressions of MMP-2 and MMP-9 were 0.226 +/- 0.012 and 2.66 +/- 0.07, protein expressions were (15.0 +/- 0.8) and (37.2 +/- 3.5) microg/L, which were all higher than those of SKOV3 without treatment of HPMC-CM (P < 0.01). Following incubation of SKOV3 with HPMC-CM(1) + antibody against Fn, mRNA expressions of MMP-2 and MMP-9 were 0.138 +/- 0.007 and 1.82 +/- 0.06, protein expressions were (8.8 +/- 0.7) and (25.8 +/- 2.5) microg/L, which decreased compared with those of HPMC-CM(1) group (P < 0.01). Following incubation of SKOV3 with HPMC-CM(2), mRNA expressions of MMP-2 and MMP-9 were 0.467 +/- 0.018 and 4.28 +/- 0.09, protein expressions were (39.3 +/- 3.6) and (62.0 +/- 5.3) microg/L, which were higher than those of HPMC-CM(1) group (P < 0.01). Following incubation of SKOV3 with HPMC-CM(3), gene expressions of MMP-2 and MMP-9 were 0.331 +/- 0.015 and 3.52 +/- 0.08, protein expressions were (27.6 +/- 1.9) and (50.0 +/- 4.1) microg/L, which decreased compared with HPMC-CM(2) group (P < 0.05), but were still higher than those of HPMC-CM(1) group (P < 0.05).

CONCLUSIONS: Ovarian carcinoma cells activate HPMC through TGF-beta1, which induces higher expressions of MMP of ovarian carcinoma cells. Up-regulating Fn expression of HPMC may be one of action mechanisms of ovarian tumor cells. Fn derived from HPMC stimulates MMP-2 and MMP-9 expressions of ovarian carcinoma cells at gene and protein levels.