Indacaterol inhibits collective cell migration and IGDQ-mediated single cell migration in metastatic breast cancer MDA-MB-231 cells.

Metastasis is the main cause of deaths related to breast cancer. This is particular the case for triple negative breast cancer. No targeted therapies are reported as efficient until now. The extracellular matrix, in particular the fibronectin type I motif IGDQ, plays a major role in regulating cell migration prior metastasis formation. This motif interacts with specific integrins inducing their activation and the migratory signal transduction.Here, we characterized the migratory phenotype of MDA-MB-231 cells, using functionalized IGDQ-exposing surfaces, and compared it to integrin A5 and integrin B3 knock-down cells. A multiomic analysis was developed that highlighted the splicing factor SRSF6 as a putative master regulator of cell migration and of integrin intracellular trafficking. Indacaterol-induced inhibition of SRSF6 provoked: i) the inhibition of collective and IGDQ-mediated cell migration and ii) ITGA5 sequestration into endosomes and lysosomes. Upon further studies, indacaterol may be a potential therapy to prevent cell migration and reduce metastasis formation in breast cancer. Video Abstract.

IGDQ motogenic peptide gradient induces directional cell migration through integrin (αv)ß3 activation in MDA-MB-231 metastatic breast cancer cells.

In the context of breast cancer metastasis study, we have shown in an in vitro model of cell migration that IGDQ-exposing (IsoLeu-Gly-Asp-Glutamine type I Fibronectin motif) monolayers (SAMs) on gold sustain the adhesion of breast cancer MDA-MB-231 cells by triggering Focal Adhesion Kinase and integrin activation. Such tunable scaffolds are used to mimic the tumor extracellular environment, inducing and controlling cell migration. The observed migratory behavior induced by the IGDQ-bearing peptide gradient along the surface allows to separate cell subpopulations with a "stationary" or "migratory" phenotype. In this work, we knocked down the integrins α5(ß1) and (αv)ß since they are already known to be implicated in cell migration. To this aim, a whole proteomic analysis was performed in beta 3 integrin (ITGB3) or alpha 5 integrin (ITGA5) knock-down MDA-MB-231 cells, in order to highlight the pathways implied in the integrin-dependent cell migration. Our results showed that i) ITGB3 depletion influenced ITGA5 mRNA expression, ii) ITGB3 and ITGA5 were both necessary for IGDQ-mediated directional single cell migration and iii) integrin (αv)ß3 was activated by IGDQ fibronectin type I motif. Finally, the proteomic analysis suggested that co-regulation of recycling transport of ITGB3 by ITGA5 is potentially necessary for directional IGDQ-mediated cell migration.

Proton irradiation orchestrates macrophage reprogramming through NFκB signaling.

Tumor-associated macrophages (TAMs) represent potential targets for anticancer treatments as these cells play critical roles in tumor progression and frequently antagonize the response to treatments. TAMs are usually associated to an M2-like phenotype, characterized by anti-inflammatory and protumoral properties. This phenotype contrasts with the M1-like macrophages, which exhibits proinflammatory, phagocytic, and antitumoral functions. As macrophages hold a high plasticity, strategies to orchestrate the reprogramming of M2-like TAMs towards a M1 antitumor phenotype offer potential therapeutic benefits. One of the most used anticancer treatments is the conventional X-ray radiotherapy (RT), but this therapy failed to reprogram TAMs towards an M1 phenotype. While protontherapy is more and more used in clinic to circumvent the side effects of conventional RT, the effects of proton irradiation on macrophages have not been investigated yet. Here we showed that M1 macrophages (THP-1 cell line) were more resistant to proton irradiation than unpolarized (M0) and M2 macrophages, which correlated with differential DNA damage detection. Moreover, proton irradiation-induced macrophage reprogramming from M2 to a mixed M1/M2 phenotype. This reprogramming required the nuclear translocation of NFκB p65 subunit as the inhibition of IκBα phosphorylation completely reverted the macrophage re-education. Altogether, the results suggest that proton irradiation promotes NFκB-mediated macrophage polarization towards M1 and opens new perspectives for macrophage targeting with charged particle therapy.

Vapor sensing with a natural photonic cell.

Photonic structures encased by a permeable envelope give rise to iridescent blue color in the scales covering the male Hoplia coerulea beetle. This structure comprises a periodic porous multilayer. The color of these scales is known for changing from blue to green upon contact with water despite the presence of the envelope. This optical system has been referred to as a photonic cell due to the role of the envelope that mediates fluid exchanges with the surrounding environment. Following from previously studied liquid-induced changes in the color appearance of H. coerulea, we measured vapor-induced color changes in its appearance. This response to vapor exposure was marked by reflectance redshift and an increase in peak reflectance intensity. Different physico-chemical processes were investigated to explain the increase in reflectance intensity, a property not usually associated with vapor-induced optical signature changes. These simulations indicated the optical response arose from physisorption of a liquid film on the beetle scales followed by liquid penetration through the envelope and the filling of micropores within the body of the photonic structure.

Quantification of nanoparticles in aqueous food matrices using Particle-Induced X-ray Emission.

Nanoparticles (NPs) of SiO(2) (15 nm) or Ag (20 - 40 nm) were dispersed in water, coffee and milk at several aqueous dilutions. The NPs dispersions concentrations were quantified with an ion beam technique: Particle-Induced X-ray Emission. Additional measurements in relation to the state of the NPs dispersions were done: particle size distribution by centrifuge liquid sedimentation and the extreme surface composition by X-ray photoelectron spectroscopy. The particle size distribution of SiO(2) and Ag NPs dispersions in water and Ag NPs in coffee remained mostly as primary particles with hydrodynamic diameters close to the reported pristine NPs diameter. SiO(2) NPs agglomerated in coffee. In milk, both NPs presented an adsorption with milk lipids. Extreme surface composition corroborated adsorption in milk and showed that SiO(2) agglomerates adsorb some coffee components. A linear tendency in the measurement of the concentration dilutions of all dispersions was measured, and a lack of media influence in the slope of each curve was found. Limits of detection with the current setup were estimated at 0.5 and 0.3 mg/ml for SiO(2) and Ag NPs, respectively.