Abstract 1244: Examining the differential roles of OSM and IL-6 in varying subtypes of breast cancer for novel therapeutic treatment

Abstract

Abstract Breast cancer remains the second leading cause of cancer-related death in women, in large part due to distant metastasis to organs such as bone, lung, liver, and brain. Our laboratory has demonstrated that the IL-6-family cytokine oncostatin M (OSM) increases circulating tumor cell (CTC) numbers and metastases to lung in vivo, and that OSM stays active when bound to proteins in the extracellular matrix, thus “bioaccumulating” in the tumor microenvironment. These published findings are supported by our results demonstrating that OSM strongly promotes expression and secretion of IL-6 from breast cancer cells. Interestingly, the increased production of IL-6 by OSM occurs only in estrogen receptor-negative (ER-) cells. It is well known that patients with ER- breast cancer, specifically triple negative breast cancer (TNBC; ER- PR- HER2-), have limited therapeutic options. However, the divergent role OSM plays in ER+ and ER- breast cancer and the mechanism by which this occurs has yet to be fully understood. Thus, we aimed to fully elucidate the difference between OSM in ER+ versus ER- breast cancer. First, we performed RNA-Seq analysis on OSM-treated human ER+ T47D cells and ER- TNBC MDA-MB-231 cells and discovered significant differences in gene expression between both cell lines upon treatment with OSM, including alteration in DNA-replication and cell cycle pathway genes. Next, to better understand the mechanism by which OSM-mediated IL-6 secretion is repressed, we utilized a computational modeling approach and evaluated the direct inhibition of STAT3 and ER to identify theoretical dimerization complex for future studies. This research aims to elucidate the unique role OSM plays in ER+ and ER- breast cancer and will provide a molecular understanding of how this occurs and will provide detailed information on which patients will benefit most from anti-OSM therapeutics. Citation Format: Cody L. Wolf, Ken Tawara, Cheryl L. Jorcyk. Examining the differential roles of OSM and IL-6 in varying subtypes of breast cancer for novel therapeutic treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1244.