We recently published a work on the glucocorticoid receptor as a key enhancer for tumor heterogeneity and metastasis. See below the press release by the University of Basel.
It has long been thought that stress contributes to cancer progression. Scientists from the University of Basel and the University Hospital of Basel have deciphered the molecular mechanisms linking breast cancer metastasis with increased stress hormones. In addition, they found that synthetic derivatives of stress hormones, which are frequently used as anti-inflammatory in cancer therapy, decrease the efficacy of chemotherapy. These results come from patient-derived models of breast cancer in mice and may have implications for the treatment of patients with breast cancer, as the researchers report in the scientific journal Nature.
Stress accelerates metastasis
To explore the heterogeneity between tumors and metastases, the researchers profiled the activity of genes in a mouse model of breast cancer. They found that metastases have increased activity of glucocorticoid receptors (GR) which mediate the effects of stress hormones such as cortisol.
Concentrations of the stress hormones cortisol and corticosterone were higher in mice with metastases that in those with no metastases. The scientists show that increased levels of these stress hormones activate the GR, which cause increased colonization and heterogeneity of the cancer cells – and ultimately, shortened survival.
Reduced efficacy of chemotherapy
GR also mediates the effects of synthetic derivatives of cortisol such as dexamethasone which is used widely to treat the side effects of chemotherapy. The research group shows that in mice with metastatic cells the efficacy of the chemotherapy drug paclitaxel was decreased when administered in combination with dexamethasone.
These findings suggest that caution should be taken when prescribing glucocorticoid hormones to patients with breast cancer. The study also suggests that GR inhibition may be beneficial for patients and could lead to the development of new therapies to combat breast cancer metastasis.
“Tumor heterogeneity is a serious hurdle for therapy. These findings highlight the importance of stress management in patients – and especially those with triple-negative breast cancer,” states Prof. Bentires-Alj. “Moderate exercise and relaxation techniques have been shown to correlate with enhanced quality of life and greater survival in patients.”
Milan M.S. Obradović, Baptiste Hamelin, Nenad Manevski, Joana Pinto Couto, Atul Sethi, Marie-May Coissieux, Simone Münst, Ryoko Okamoto, Hubertus Kohler, Alexander Schmidt, Mohamed Bentires-Alj
Glucocorticoids promote breast cancer metastasis
Nature (2019), doi: 10.1038/s41586-019-1019-4
Congratulations to Ana Luisa Correia for the Hans-Joerg Senn BBC award 2018.
Thank you to Mr Kamal Lakhdar (Moroccan painter) for the generous painting that represents tumor heterogeneity: the thread connecting the research of our team!
Molecular biologist by training, Charly splits his studies between the University of Rennes 1 and Lyon 1 in France. After a master degree in molecular and cellular oncology, he started a 3 years PhD at the IRSET Institute, in Rennes, under the supervision of Dr Denis Michel. His research focused on estrogen receptor alpha and aimed to better understand how micro environmental hypoxia can drive hormone resistance in breast cancer cells. He also identified MKL1, a transcriptional co-activator activated after E-Cadherin disruption, capable of converting epithelial luminal to basal cell identity, thereby enhancing tumor cell malignancy. After defending his PhD last December, Charly left the softness of Brittany for this exciting challenge as Post-doc in Momo’s lab where he will be working on epigenetic mechanisms underpinning tumor cell heterogeneity and anti-cancer drug resistance.