Abstract B08: Inflammasome components caspase-1, IL1β, IL18 and NLRP3 (NOD-like receptor family, pyrin domain containing 3) are increased in a spontaneous model (chicken: Gallus gallus) of human ovarian cancer

Abstract

Abstract Chronic inflammation is associated with cancer risk and development. There is increasing evidence that a chronic, pro-inflammatory environment is mediated by multi-protein inflammasome complexes that promote activation of IL1β and IL18, which are apex cytokines for regulation of inflammation. The objective was to determine if the inflammasome components NLRP3, caspase-1, IL1β and IL18 were expressed in ovarian cancer and if the expression differed between normal ovary and ovarian tumors using the hen, an animal model of spontaneous ovarian cancer. mRNA was measured by qRT-PCR using primers based on chicken orthologs of human genes from the NCBI database as follows, NLRP3 XM_001233261.3; Caspase-1 XM_003642384.2; IL1β NM_204524.1; IL18 NM_204608; IL17 NM_204460.1. mRNA expression (mean fold change compared to normal ovary = mFC) was increased significantly (t -test) compared to normal ovaries for caspase-1 (mFC=14.6±12.6; p=0.01), IL1β (mFC=6.5±5.3 p=0.01) and IL18 (mean fold change=4.9±3.4; p=0.01) with a moderate increase in NLRP3 (mFC=1.7±0.98; p=0.04) in cancer (n=8) compared to normal ovary (n=6). Expression of the pro-inflammatory cytokine, IL17 was increased (mFC=4.0±6.0; p=0.1) but not significantly in this limited sample set. Moderate protein expression of the same components was evident by immunohistochemistry in groups of tumor cells but not in all tumor cells. Expression also occurred in tumor immune cells; the number of immunohistochemically reactive immune cells varied among tumors. Differences in invading immune cells with an activated inflammasome could account for the range of total mRNA values; differences among tumor expression of inflammasomes infers a potential basis for differences in response to immunotherapies. The results demonstrate expression of inflammasome components in a spontaneous model resembling human ovarian cancer and suggest a mechanism by which a chronic pro-inflammatory, pro-tumor environment is maintained. Improved understanding of the role of inflammasomes could lead to methods for management of the tumor immune environment and responses to immunotherapy. Citation Format: Judith Luborsky, Seara Edassery, Seby L. Edassery, Animesh Barua, Janice M. Bahr. Inflammasome components caspase-1, IL1β, IL18 and NLRP3 (NOD-like receptor family, pyrin domain containing 3) are increased in a spontaneous model (chicken: Gallus gallus) of human ovarian cancer. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr B08.