DIRECT TUMORICIDAL FUNCTION AGAINST HUMAN OVARIAN-CARCINOMA BY INTERFERON-GAMMA-ACTIVATED AND TUMOR NECROSIS FACTOR-ALPHA-ACTIVATED HUMAN PERITONEAL MESOTHELIAL CELLS

We report in this study that human peritoneal mesothelial cells can ly se human malignant ovarian cells. Recombinant human interferon (IFN)-g amma and rhTNF-alpha significantly activated cytotoxicity of mesotheli al cells against the tumor necrosis factor (TNF)-resistant SK-OV-3 cel l line, Cytotoxicity was measured by Cr-51-release and was also confir med by 3-(4,5-dimethylthiazol-2-yl)-2,5-dipheny tetrazaloium bromide ( MTT) assay and visual assessment. Lysis of SK-OV-3 by rhIFN-gamma and rhTNF-alpha-activated mesothelial cells was dose-responsive with highe st levels of anti-tumor activity expressed at 10(3) IU ml(-1) of each respective cytokine. Both rhIFN-gamma and rhTNF-alpha-stimulated mesot helial cells were able to independently lyse the malignant ovarian tar gets 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 cyto toxicity expressed by rhIFN-alpha-activated mesothelial cells in this report was independent of TNF target sensitivity, rhTNF-alpha itself w as able to stimulate mesothelial cytotoxic function. These results, ta ken together, emphasize the need to better define the role, and theref ore, potential therapeutic implications of, mesothelial cells in local carcinogenic processes.