Binding of CD157 protein to fibronectin regulates cell adhesion and spreading

CD157/BST-1 behaves both as an ectoenzyme and signaling receptor and is an important regulator of leukocyte trafficking and ovarian cancer progression. However, the molecular interactions underpinning the role of CD157 in these processes remain obscure. The biological functions of CD157 and its partnership with members of the integrin family prompted us to assume the existence of a direct interaction between CD157 and an unknown component of the extracellular matrix. Using solid-phase binding assays and surface plasmon resonance analysis, we demonstrated that CD157 binds fibronectin with high affinity within its heparin-binding domains 1 and 2. Furthermore, we found that CD157 binds to other extracellular matrix proteins containing heparin-binding domains. Finally, we proved that the CD157-fibronectin interaction occurs with living cells, where it elicits CD157-mediated cell responses. Indeed, knockdown of CD157 in Met-5A mesothelial cells changed their morphology and cytoskeleton organization and attenuated the activation of intracellular signaling pathways triggered by fibronectin. This led to impaired cell spreading and adhesion to selected extracellular matrix proteins. Collectively, these findings indicate a central role of CD157 in cell-extracellular matrix interactions and make CD157 an attractive therapeutic target in inflammation and cancer

Inside the Michelangelo effect: The role of art and aesthetic attractiveness on perceived fatigue and hand kinematics in virtual painting

It has recently been discovered that during a virtual reality task of painting, if the subjects have the illusion of recreating an artistic masterpiece, they improve their performances and perceive less fatigue compared to simply coloring a virtual canvas. This phenomenon has been called the Michelangelo effect. However, it was unclear if this effect was related to the aesthetic experience of beauty or if it was specific to artistic stimuli. To clarify this point, 26 healthy subjects performed the virtual task of erasing a blank sheet on the canvas, revealing an image that could be a painting or a photo, classified as beautiful or not. Beautiful paintings were famous artistic portraits, non-beautiful paintings were rough reproductions of them. Photos of popular people were matched with paintings according to their similarity for somatic traits, posture, and clothes. Beautiful and non-beautiful photos were classified according to whether the pictured person was famous or not for their beauty. For each stimulus the objective beauty, subjective beauty, and effort to complete the task perceived by the subject were self-assessed on a numerical rating scale, recorded and analyzed. Furthermore, the hand kinematic trajectory was instrumentally recorded and its spatiotemporal parameters were computed. Less fatigue was perceived for the paintings than for the photos (p = .020), but not for beautiful versus non-beautiful stimuli (p = .325). Only in the artistic stimuli, subjective beauty was found to be negatively correlated with perceived fatigue (p = .030) and performed errors (p = .005). The kinematic parameters were found to be affected by the interactions between the gender of the participant and that of the person in the photo. These results supported the idea that the Michelangelo effect was stronger when subjects interacted with artefacts, modulated by the perceived beauty of the artistic stimulus

Overexpression of CD157 contributes to epithelial ovarian cancer progression by promoting mesenchymal differentiation

Epithelial ovarian carcinoma (EOC) is an aggressive tumor often diagnosed at an advanced stage, when there is little or no prospect of cure. Despite advances in surgical and chemotherapeutic strategies, only marginal improvements in patient outcome have been obtained. Hence, unraveling the biological mechanisms underpinning EOC progression is critical for improving patients’ survival. Recently, we reported that CD157 (an ectoenzyme regulating leukocyte diapedesis) is expressed in EOC and that high expression of the molecule is negatively correlated with the disease outcome in patients. Here, we demonstrate that forced overexpression of CD157 in OVCAR-3, TOV-21G, A2780 and OV-90 ovarian cancer cell lines promotes morphological and phenotypic changes characterized by disruption of intercellular junctions, downregulation of epithelial markers and upregulation of mesenchymal ones. These changes in cell shape and phenotype bring to reduced sensitivity to anoikis, increased anchorage-independent growth, cell motility and mesothelial invasion. Conversely, knockdown of CD157 in OV-90 and OC314 cells reverts the mesenchymal phenotype and reduces the cells’ migratory potential. Transcriptome profiling analysis highlighted 378 significantly differentially expressed genes, representing the signature of CD157-overexpressing OVCAR-3 and OV-90 cells. The modulation of selected genes translates into alteration of protein expression that give cells a highly malignant phenotype. The overall picture deduced from the analysis of the modulated transcripts is that high expression of CD157 strengthens a number of biological processes favoring tumor progression (including development and cell motility), and weakens several biological processes hindering tumor progression (such as apoptosis, cell death and response to stress). Together, these findings implicate CD157 in the progression of EOC to metastatic disease and suggest that CD157 may represent a valuable therapeutic target