Objectives: The objectives of this study were to determine (1) the frequency of expression of the interleukin-11 receptor alpha subunit (IL-11Ralpha) and its signal transducing subunit, gp130, among primary ovarian carcinomas; (2) the frequency of expression of IL-11 in ovarian carcinomas; and (3) the potential role IL-11 might have in ovarian cancer cell biology.
Methods: An immunohistochemical assay was used to determine the expression of IL-11Ralpha and the gp130 cofactor among primary ovarian carcinomas; the expression of IL-11 in ovarian malignancies was determined using reverse transcription polymerase chain reaction (RT-PCR). The ability of IL-11 to stimulate [3H]thymidine incorporation in IL-11R-expressing ovarian carcinoma cell lines (OVCAR-3 and SKOV-3) and/or abrogate cell death mediated by apoptosis-inducing agents using an ELISA assay that quantitates DNA fragmentation was also studied.
Results: IL-11Ralpha was expressed in the malignant epithelial cells of 45 of 48 (93.8%) primary ovarian carcinoma samples studied. In 45 primary ovarian carcinoma samples where both components of the IL-11 receptor (IL-11Ralpha and gp130) were examined, coexpression was observed in 42 (93.3%). Expression of the IL-11 receptor components was also found in the stromal layer. Coexpression of IL-11Ralpha and gp130 was commonly observed in both benign ovarian tumors and in the epithelial layer of normal ovaries. In contrast, IL-11 mRNA was expressed in only 3 of 21 malignant samples studied (14.3%). Recombinant human IL-11 was unable either to stimulate [3H]thymidine incorporation or to block cell death effected by paclitaxel or Fas-activating antibodies in in vitro assays using OVCAR -3 or SKOV-3 cells.
Conclusions: The IL-11 receptor system is commonly expressed in both malignant and nonmalignant ovarian tissues, although its function in ovarian epithelial cell biology remains unclear.