Analysis Of Il-18 Expression And Function In Human Ovarian Cancer Cell Lines And Normal Ovarian Epithelium

1. Functional analysis of IL-18 expression in human ovarian tumor cellsIL-18 is a novel pro-inflammatory cytokine that may play an important role in inducing EFN- production in both activated NK cells and T cells. Considering the possible application of IL-18 for tumor immunotherapy and the proposed use of IL-18 in cancer immune/gene therapy, we have studied the expression of IL-18 in tumor cell. By RT-PCR IL-18 mRNA was detected in all the human ovarian carcinoma cell lines so far tested (9/9) and in one half of tumour cell populations obtained from ovarian carcinoma patients (4/8). ICE mRNA was expressed in a smaller fraction of samples (3/9 cell lines and 3/8 samples from patients). IL-18 protein was also found in 7/13 ovarian carcinoma solid tumours by immunohistochemical analysis. In tumour cell lines we were able to detect abundant intracellular pro-IL-18 (24kDa) by Western blotting, whereas the mature form of EL-18 was undetectable, irrespective of the presence of ICE mRNA and protein. Only pro-IL-18 was also found in the cultured ovarian carcinoma cell lines supernatants, which did not display any IL-18 biological activity in functional assays. Cultured normal ovarian epithelial cells revealed the presence of both IL-18 and ICE mRNA in all samples (5/5), and IL-18 protein was expressed by the thin epithelial cell layer surrounding normal ovary. More importantly, normal ovarian epithelial cells released low but detectable amounts ofmature IL-18 in the culture supernatant, which displayed IL-18-like biological activity in functional assays. These data suggest that the production of mature biologically active IL-18 is a feature of the normal ovarian surface epithelium but lost during neoplastic transformation.