The glucocorticoid receptor (GR) has emerged as a pivotal player in influencing cell migration dynamics, particularly within the complex and varied landscapes of breast cancer. New research led by Pósa et al. sheds light on how activation of this receptor by glucocorticoids, namely the agonist dexamethasone (dex), affects the behavior of estrogen receptor-positive (ER+) breast cancer cells differently compared to triple-negative (TN) variants. This study highlights the nuanced role of GR, emphasizing its significant impact on tumor progression.
Breast cancer is the most commonly diagnosed form of cancer among women globally, with over two million new cases recorded each year. Comprised of various subtypes, breast cancer presents unique clinical challenges, particularly with patients exhibiting TN tumors, which lack estrogen receptors and are associated with poorer prognoses. Treatment strategies often involve glucocorticoids like dex to manage chemotherapy-induced side effects. Yet, researchers have expressed concerns about glucocorticoids potentially promoting cancer cell growth, particularly among TN tumors.
To investigate the dual effects of glucocorticoids, researchers utilized both two-dimensional (2D) and three-dimensional (3D) culture systems, examining the impacts of dex on cellular proliferation and migration. Their findings indicate nuanced responses, with dex enhancing proliferation and motility of TN breast cancer cells, whereas it reduced cell growth in ER+ lines. Specifically, dex augmented cell motility after 4-6 hours post-treatment, with initial inhibitory effects observed after just two hours.
To gain greater insight, the authors performed transcriptome sequencing, which identified significant differences between gene expressions of ER+ and TN breast cancer cells. This analysis revealed alterations related to cell adhesion and extracellular matrix signaling pathways tied to GR activity. “The effects of dexamethasone on breast cancer cell migration are influenced by ER status and treatment duration,” the researchers concluded, emphasizing the complexity of GR's role.
Particularly intriguing were observations related to cell migration dynamics, illuminating how GR activation can induce significant changes. Time-lapse imaging demonstrated distinct migration characteristics, highlighting heterogeneous responses among TN cell lines. The study also noted, “Dexamethasone-induced migration phenotype was not rescued by mifepristone,” indicating potential non-genomic actions of GR not influenced merely by transcriptional mechanisms.
These findings are clinically relevant as they underline the importance of considering GR activation when administering glucocorticoids during cancer treatment. The interaction between GR and other cellular pathways emphasizes the necessity for personalized treatment approaches for breast cancer patients, especially those with aggressive TN subtypes. This study not only adds to the growing body of literature surrounding glucocorticoid effects but also sets the groundwork for future exploration of targeted therapies aimed at mitigating the metastatic potential of aggressive breast cancer forms.
The research urges continued investigation of GR's diverse roles, particularly within the contexts of different breast cancer subtypes, to develop effective strategies for optimizing treatment regimens moving forward.