Metastatic progression of epithelial ovarian cancer (EOC) involves the partial epithelial-to-mesenchymal transition (EMT) of cancer cells in the primary tumor and dissemination into peritoneal fluid. In part to the high degree of heterogeneity in EOC cells, the identification of EMT in highly epithelial cells in response to differences in matrix mechanics, growth factor signaling, and tissue hypoxia is very difficult. We analyzed different degrees of EMT by tracking changes in cell and nuclear morphology, along with the organization of cytoskeletal proteins. In our analysis, we see a small percentage of individual cells that show dramatic response to TGF-β1 and hypoxia treatment. We demonstrate that EOC cells are spatially aware of their surroundings, with a subpopulation of EOC cells at the periphery of a cell cluster in 2D environments exhibited a greater degree of EMT. These peripheral cancer cells underwent partial EMT, displaying a hybrid of mesenchymal and epithelial characteristics, which often included less cortical actin and more perinuclear cytokeratin expression. Collectively, these data show that tumor-promoting microenvironment conditions can mediate invasive cell behavior in a spatially regulated context in a small subpopulation of highly epithelial clustered cancer cells that maintain epithelial characteristics while also acquiring some mesenchymal traits through partial EMT.

Extensive characterization of B cell receptor repertoires across six immune-mediated diseases reveals novel insights into disease pathogenesis.

It is with great pleasure that we read the work by Mikuls and colleagues (1) regarding pertinent consensus-based guidelines for managing rheumatic diseases under the context of COVID-19. We would first like to note that our nationwide retrospective cohort studies have shown that hydroxychloroquine treatment not only presents no increased risk of cardiac arrythmia in multiple rheumatic diseases (2), but also likely provides cardiovascular protection (3). Therefore, we believe the task force should reconsider the implications of halting hydroxychloroquine treatment in the context of SARS-CoV-2 infection.