Glucocorticoids induce CCN5/WISP-2 expression and attenuate invasion in oestrogen receptor-negative human breast cancer cells.

CCN5 (cysteine-rich 61/connective tissue growth factor/nephroblastoma overexpressed 5)/WISP-2 [WNT1 (wingless-type MMTV integration site family, member 1)-inducible signalling pathway protein 2] is an oestrogen-regulated member of the CCN family. CCN5 is a transcriptional repressor of genes associated with the EMT (epithelial-mesenchymal transition) and plays an important role in maintenance of the differentiated phenotype in ER (oestrogen receptor)-positive breast cancer cells. In contrast, CCN5 is undetectable in more aggressive ER-negative breast cancer cells. We now report that CCN5 is induced in ER-negative breast cancer cells such as MDA-MB-231 following glucocorticoid exposure, due to interaction of the endogenous glucocorticoid receptor with a functional glucocorticoid-response element in the CCN5 gene promoter. Glucocorticoid treatment of MDA-MB-231 cells is accompanied by morphological alterations, decreased invasiveness and attenuated expression of mesenchymal markers, including vimentin, cadherin 11 and ZEB1 (zinc finger E-box binding homeobox 1). Interestingly, glucocorticoid exposure did not increase CCN5 expression in ER-positive breast cancer cells, but rather down-regulated ER expression, thereby attenuating oestrogen pathway signalling. Taken together, our results indicate that glucocorticoid treatment of ER-negative breast cancer cells induces high levels of CCN5 expression and is accompanied by the appearance of a more differentiated and less invasive epithelial phenotype. These findings propose a novel therapeutic strategy for high-risk breast cancer patients.

Cataloging Existing Hearing Loss Cohort Data to Guide the Development of Precision Medicine for Sensorineural Hearing Loss: A Systematic Review of Hearing Repositories.

Recent breakthroughs in our understanding of sensorineural hearing loss etiology have encouraged the identification of novel hearing therapeutics, paving the way for precision hearing medicine. Critical to this field is the curation of health resources on hearing data. A systematic review of the literature was conducted to map existing (inter)national and regional datasets that include hearing data to inform the development of future hearing repositories. Systematic literature review was performed adhering to Preferred Reporting Items for Systematic Review and MetaAnalysis recommendations. Databases, including those from gray literature, were searched to identify publications reporting on phenotypic and/ or genotypic hearing data in May 2019. The databases reviewed were Medline, PubMed, Embase databases, and Google Scholar. Publications on local datasets were excluded. All hearing datasets identified in the screening process were noted. For each dataset, geography, context, objective, period of time run, numbers and demographics of participants, genomic data, hearing measures and instruments used were extracted and cataloged. One hundred and eighty-eight datasets were identified, containing hearing data on populations ranging from 100 to 1.39 million individuals, and all extracted data have been cataloged. This searchable resource has been made accessible online. This unique catalog provides an overview of existing datasets that contain valuable information on hearing. This can be used to inform the development of national and international patient data repositories for hearing loss and guide strategic collaboration between key stakeholder groups, pivotal to the delivery and development of sensorineural hearing loss precision diagnostics and treatments.

A Model of Chronic Exposure to Unpredictable Mild Socio-Environmental Stressors Replicates Some Spaceflight-Induced Immunological Changes.

During spaceflight, astronauts face radiations, mechanical, and socio-environmental stressors. To determine the impact of chronic socio-environmental stressors on immunity, we exposed adult male mice to chronic unpredictable mild psychosocial and environmental stressors (CUMS model) for 3 weeks. This duration was chosen to simulate a long flight at the human scale. Our data show that this combination of stressors induces an increase of serum IgA, a reduction of normalized splenic mass and tends to reduce the production of pro-inflammatory cytokines, as previously reported during or after space missions. However, CUMS did not modify major splenic lymphocyte sub-populations and the proliferative responses of splenocytes suggesting that these changes could be due to other factors such as gravity changes. Thus, CUMS, which is an easy to implement model, could contribute to deepen our understanding of some spaceflight-associated immune alterations and could be useful to test countermeasures.