Abstract
Abstract As part of our immune response, the body produces anti-tumorigenic inflammatory proteins to kill cancer cells. However, cancer cells can usurp chronic inflammation for their own survival. Interleukin-1 (IL-1) is an inflammatory protein found in breast cancer (BCa) tumors that is elevated in the BCa patient tumors and serum and promotes metastasis, indicating IL-1 is clinically relevant. But the molecular mechanisms underlying the effect of chronic IL-1 on BCa progression remain unknown. We previously discovered that acute exposure to IL-1 represses essential hormone receptors in cancers cells, but concomitantly upregulates other compensatory pro-survival proteins that contribute to tumor progression. To determine if chronic IL-1 inflammation has the same effect, we generated cell subline models using the human breast cancer cell line, T47D, by exposing T47D cells chronically to IL-1 for several months. Notably, we found that the T47D chronic IL-1 sublines stably evolve insensitivity to exogenous IL-1. This result suggests that chronic IL-1 causes stable molecular changes that may affect cancer cell response to exogenous factors.Therapeutic strategies include blocking exogenous hormone or growth factor signals in the tumor microenvironment to attenuate cancer cell growth, proliferation, and survival. Therefore, we grew T47D parental and chronic IL-1 sublines in the absence of serum to determine the effect of chronic IL-1 exposure on BCa cell response to hormone and growth factor inhibition. Preliminarily, we do not observe differences in parental versus subline response to serum starvation, suggesting that differential response to exogenous factors is specific to IL-1 signaling. To better understand how chronic IL-1 -induced molecular changes effect BCa cell response to the tumor microenvironment, we will perform sequencing and bioinformatics analysis to identify IL-1 -dependent and/or independent signaling pathways stably altered in the chronic IL-1 sublines. Citation Format: Roopal Dhar, Ola M. Olaleye, Rana Tarig Abdelaziz, Jyotsna Tera Reddy, Nikki Delk. Investigation of the effect of chronic IL-1 exposure on breast cancer cell line response to external signaling factors [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 2569.
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