Colon cancer-derived myofibroblasts increase endothelial cell migration by glucocorticoid-sensitive secretion of a pro-migratory factor

AbstractAngiogenesis is important in cancer progression and can be influenced by tumor-associated myofibroblasts. We addressed the hypothesis that glucocorticoids indirectly affect angiogenesis by altering the release of pro-angiogenic factors from colon cancer-derived myofibroblasts.Our study shows that glucocorticoids reduced prostanoids, urokinase-type plasminogen activator (uPA) and angiopoietin-like protein-2 (ANGPTL2) levels, but increased angiogenin (ANG) in supernatant from human CT5.3hTERT colon cancer-derived myofibroblasts. Conditioned medium from solvent- (CMS) and dexamethasone (Dex)-treated (CMD) myofibroblasts increased human umbilical vein endothelial cell (HUVEC) proliferation, but did not affect expression of pro-angiogenic factors or tube-like structure formation (by HUVECs or human aortic ECs). In a HUVEC scratch assay CMS-induced acceleration of wound healing was blunted by CMD treatment. Moreover, CMS-induced neovessel growth in mouse aortic rings ex vivo was also blunted using CMD. The latter effect could be ascribed to both Dex-driven reduction of secreted factors and potential residual Dex present in CMD (indicated using a dexamethasone-spiked CMS control). A similar control in the scratch assay, however, revealed that altered levels of factors in the CMD, and not potential residual Dex, were responsible for decreased wound closure.In conclusion, our results suggest that glucocorticoids indirectly alter endothelial cell function during tumor development in vivo

MISpheroID: a knowledgebase and transparency tool for minimum information in spheroid identity

Spheroids are three-dimensional cellular models with widespread basic and translational application across academia and industry. However, methodological transparency and guidelines for spheroid research have not yet been established. The MISpheroID Consortium developed a crowdsourcing knowledgebase that assembles the experimental parameters of 3,058 published spheroid-related experiments. Interrogation of this knowledgebase identified heterogeneity in the methodological setup of spheroids. Empirical evaluation and interlaboratory validation of selected variations in spheroid methodology revealed diverse impacts on spheroid metrics. To facilitate interpretation, stimulate transparency and increase awareness, the Consortium defines the MISpheroID string, a minimum set of experimental parameters required to report spheroid research. Thus, MISpheroID combines a valuable resource and a tool for three-dimensional cellular models to mine experimental parameters and to improve reproducibility. © 2021, The Author(s)

The emergence of institutions in Hayek’s theory: two views or one?

Hayek opposes the explanation of the emergence of institutions as “spontaneous (unintentional) order”, which he considers correct, against “constructivism” (viewed as erroneous). This dichotomy exhibits some inconsistencies, for, on Hayek’s account, constructivist ideologies seem able both to prevent the evolutionary emergence of norms and to generate institutions coherent with deliberate, intentional, purposes. If this is so, are there then two views on the emergence of institutions in Hayek’s theory? The paper consequently discusses whether constructivism and evolution of norms are two alternative kinds of explanation, and in particular whether the former can be interpreted in evolutionary terms. Copyright Springer Science+Business Media, LLC 2006Spontaneous order, Constructivism, Evolution of norms, Institutions, B4, B25,