Glucocorticoid receptor antagonism and beta adrenergic receptor inhibition: Implications in triple-negative breast cancer brain metastasis

Andra Antohi, Melanie Flint, Andrew E. Greenstein, Hazel Hunt

Research output: Chapter in Book/Conference proceeding with ISSN or ISBNConference contribution with ISSN or ISBNpeer-review


Triple-negative breast cancer (TNBC) brain metastasis is a major clinical challenge, and the role of stress hormone receptors, specifically the glucocorticoid receptor (GR) and beta-adrenergic receptor (β-AR), in cancer progression remains unclear. This study investigates the impact of GR and β-AR antagonism on the modulation of astrocyte-cancer cell interactions in the context of TNBC brain metastasis.
Primary murine astrocytes were isolated and cultured alone or in co-culture with 4T1 breast cancer cells. Stress hormones, their antagonists, or a combination of both were administered to the cells for 24 hours. Following treatment, the cell lysates were subjected to western blotting, and the media were analyzed using enzyme-linked immunosorbent assays (ELISAs). ELISAs measured the levels of TNF-alpha, IL-6, and CXCL10.
When cultured alone, astrocytes exhibited a significant (p<0.05) increase in IL-6 expression upon treatment with both stress hormones. The addition of GR and β-AR inhibitors mitigated this effect. While TNF-alpha expression was elevated in hormone-treated cells, it did not reach statistical significance. CXCL10 expression significantly decreased in cells treated with both stress hormones and their inhibitors compared to the control (p<0.005). In the co-culture setting, astrocyte-released cytokines (IL-6, CXCL10, TNF-alpha). were significantly reduced in control samples.
Glucocorticoid receptor antagonism and beta-adrenergic receptor inhibition exerted modulatory effects on astrocyte-cancer cell interactions. The upregulation of IL-6 in astrocytes upon stress hormone exposure suggests its potential role in promoting TNBC brain metastasis. Furthermore, the significant decrease in CXCL10 expression following combined hormone and inhibitor treatment highlights its potential as a therapeutic target. These findings provide insights into the complex interplay between stress hormone receptors and cancer progression in the context of TNBC brain metastasis.
Original languageEnglish
Title of host publicationAnnals of oncology
Number of pages1
ISBN (Print)0923-7534
Publication statusPublished - 1 Oct 2023


  • stress, cortisol, astrocytes


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