PMID- 11948465 OWN - NLM STAT- MEDLINE DCOM- 20020501 LR - 20190708 IS - 0020-7136 (Print) IS - 0020-7136 (Linking) VI - 98 IP - 6 DP - 2002 Apr 20 TI - Expression of interleukin-18 in human ovarian carcinoma and normal ovarian epithelium: evidence for defective processing in tumor cells. PG - 873-8 AB - Interleukin-18 (IL-18) is a proinflammatory monokine structurally related to IL-1beta that stimulates interferon-gamma (IFN-gamma) production. IL-18 is synthesized as an inactive precursor, pro-IL-18, which is cleaved by IL-1beta-converting enzyme (ICE)/caspase-1 in a mature protein. In view of the proposed use of IL-18 in cancer immuno/gene therapy, we have studied the expression of IL-18 in tumor cells. IL-18 mRNA was detected by reverse transcriptase polymerase chain reaction in all human ovarian carcinoma cell lines tested (9/9) and in one-half of tumor 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 tumors by immunohistochemic analysis. In tumor cell lines we were able to detect abundant intracellular pro-IL-18 (24 kDa) by Western blotting, whereas the mature form of IL-18 was undetectable, irrespective of the presence of ICE mRNA and protein. Only pro-IL-18 was also found in the ovarian carcinoma cell supernatants, which did not display any IL-18 biologic activity in functional assays. Normal cultured 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 of mature IL-18 in the culture supernatant, which displayed IL-18-like biologic activity in functional assays. These data suggest that mature biologically active IL-18 production is a feature of the normal ovarian surface epithelium lost during neoplastic transformation. CI - Copyright 2002 Wiley-Liss, Inc. FAU - Wang, Zhao Yuan AU - Wang ZY AD - Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy. FAU - Gaggero, Alessia AU - Gaggero A FAU - Rubartelli, Anna AU - Rubartelli A FAU - Rosso, Ombretta AU - Rosso O FAU - Miotti, Silvia AU - Miotti S FAU - Mezzanzanica, Delia AU - Mezzanzanica D FAU - Canevari, Silvana AU - Canevari S FAU - Ferrini, Silvano AU - Ferrini S LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Int J Cancer JT - International journal of cancer JID - 0042124 RN - 0 (DNA Primers) RN - 0 (Interleukin-18) RN - 0 (RNA, Messenger) RN - EC 3.4.22.36 (Caspase 1) SB - IM MH - Blotting, Western MH - Carcinoma, Endometrioid/genetics/*metabolism/pathology MH - Caspase 1/genetics/metabolism MH - Cells, Cultured MH - Cystadenocarcinoma, Serous/genetics/*metabolism/pathology MH - DNA Primers/chemistry MH - Enzyme-Linked Immunosorbent Assay MH - Epithelial Cells/metabolism MH - Female MH - Humans MH - Immunoenzyme Techniques MH - Interleukin-18/genetics/*metabolism MH - Ovarian Neoplasms/genetics/*metabolism/pathology MH - Ovary/*metabolism MH - RNA, Messenger/analysis MH - Reverse Transcriptase Polymerase Chain Reaction EDAT- 2002/04/12 10:00 MHDA- 2002/05/02 10:01 CRDT- 2002/04/12 10:00 PHST- 2002/04/12 10:00 [pubmed] PHST- 2002/05/02 10:01 [medline] PHST- 2002/04/12 10:00 [entrez] AID - 10.1002/ijc.10268 [pii] AID - 10.1002/ijc.10268 [doi] PST - ppublish SO - Int J Cancer. 2002 Apr 20;98(6):873-8. doi: 10.1002/ijc.10268.