Abstract

We report in this study that human peritoneal mesothelial cells can lyse human malignant ovarian cells. Recombinant human interferon (IFN)-γ and rhTNF-α significantly activated cytotoxicity of mesothelial cells against the tumor necrosis factor (TNF)-resistant SK-OV-3 cell line. Cytotoxicity was measured by ⁵¹Cr-release and was also confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazaloium bromide (MTT) assay and visual assessment. Lysis of SK-OV-3 by rhIFN-γ and rhTNF-α-activated mesothelial cells was dose-responsive with highest levels of anti-tumor activity expressed at 10³ IU ml^-1 of each respective cytokine. Both rhIFN-γ and rhTNF-α-stimulated mesothelial cells were able to independently lyse the malignant ovarian targets in the abscence of the activating cytokines. In a previous study we have described mesothelial cell lysis of a cervical carcinoma cell line through a TNF-dependent mechanism. Although the mechanism of cytotoxicity expressed by rhIFN-α-activated mesothelial cells in this report was independent of TNF target sensitivity, rhTNF-α itself was able to stimulate mesothelial cytotoxic function. These results, taken together, emphasize the need to better define the role, and therefore, potential therapeutic implications of, mesothelial cells in local carcinogenic processes.