DIRECT TUMORICIDAL FUNCTION AGAINST HUMAN OVARIAN-CARCINOMA BY INTERFERON-GAMMA-ACTIVATED AND TUMOR NECROSIS FACTOR-ALPHA-ACTIVATED HUMAN PERITONEAL MESOTHELIAL CELLS
Mb. Michelininorris et al., DIRECT TUMORICIDAL FUNCTION AGAINST HUMAN OVARIAN-CARCINOMA BY INTERFERON-GAMMA-ACTIVATED AND TUMOR NECROSIS FACTOR-ALPHA-ACTIVATED HUMAN PERITONEAL MESOTHELIAL CELLS, International journal of gynecological cancer, 6(1), 1996, pp. 27-37
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.