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Purinergic signaling plays a crucial role in vascular endothelium functions. In particular, ionotropic P2X receptors (P2XRs) are engaged in various intracellular pathways through which endothelial cells (ECs) adapt to external stimuli. However, very little is known about the impact of P2XRs on vascular remodeling during carcinogenesis. We previously demonstrated that high purinergic stimulation impairs the migratory phenotype of tumor-derived endothelial cells (TECs) but not of normal ECs. Since P2XRs are sensitive to different physical and chemical factors, we investigated the impact of tumor microenvironment (TME) on healthy ECs to verify the ability of cancer cells to affect endothelial migratory phenotype through purinergic signaling tuning. More specifically, we focused on P2XR modulation by two different types of TME, mimicking breast and pancreas cancer milieux, which show very different features in terms of vascularization and composition. ECs conditioning with both cancer cell types induced a significant upregulation of some of the most represented P2XR. However, only conditioning with MCF-7 cells and not that with PANC-1 cells was able to alter the migratory phenotype of normal ECs supporting a P2XR-mediated inhibition of cell migration. The differences observed between the two cancer cells could be due to their different proliferative potential and the subsequent different extracellular pH. In addition, in agreement with some of our previous data, the P2XR-induced inhibition of EC migration seems to be independent of calcium signals, as conditioned ECs didn't reveal any changes in the long-lasting responses evoked by purinergic agonists. Collectively, highlighting a significant P2RX modulation by TME, our data strengthen the hypothesis that purinergic signaling may play a central role in vascular remodeling during carcinogenesis. However, the molecular routes upstream and downstream of this modulation remain to be elucidated. [ABSTRACT FROM AUTHOR]

• Four dental implant surfaces tested for protein adsorption and cell adhesion. • The dispersive to polar surface energy ratio seems predictive of biological outcome. • β1 integrin and transient receptor potential vanilloid4 (TRPV4) dictate cell adhesion. This paper aimed to assess how four different and representative dental implant surfaces (machined MAC, grit blasted GB, acid etched AE and grit blasted acid etched GBAE) could affect cell adhesion possibly modulating protein adsorption and a paramount cell receptor such as α5ß1 integrin. Based on non-contact 3D profilometry, GBAE was rougher than the other surfaces, while GB and AE reached similar intermediate S a values and MAC resulted the smoothest one. According to X-ray Photoelectron Spectroscopy and Raman spectroscopy, all the surfaces showed amorphous titania with similar amounts of carbon contaminants. The lesser protein adsorption and delayed cell adhesion of GB, which did not hinder cell proliferation, were correlated to the altered dispersive to polar SE ratio, that was at least double-fold for GB (2.6) compared to MAC (0.8), SL (1.3) and AE (1.2). The biological response in vitro relied on β1 integrin activation that cooperated with the putative mechano-protein transient receptor potential vanilloid 4 (TRPV4) in determining the adhesion of the osteoblasts. In fact, it could be rescued by over activating β1 integrin. On the other hand, silencing TRPV4 strongly inhibited cell adhesion on selected substrates, proving the role of this protein in mediating osteoblasts adhesion on titanium substrates. [ABSTRACT FROM AUTHOR]