Physiological type I collagen organization induces the formation of a novel class of linear invadosomes

International audienceAbbreviations used: BAEC, bovine aortic endothelial cell; BHK-21, baby hamster kidney cell line; DDR, discoidin domain receptor; DPBS, Dulbecco's phosphate-buffered saline; ECM, extracellular matrix; FCS, fetal calf serum; FITC, fluorescein isothiocyanate; GFP, green fluorescent protein; GPVI, glycoprotein VI; HFF, human foreskin fibroblast; HPAEC, human pulmonary arterial endothelial cell; HUVEC, human umbilical vein endothelial cell; IRM, interference reflection microscopy; LAIR-1, leukocyte-associated immunoglobulin-like receptor-1; LSEC, liver sinusoi-dal endothelial cell; MEF, mouse embryonic fibroblast; MMP, matrix metallopro-teinase; MT1-MMP, membrane type 1 matrix metalloproteinase; NA, numerical aperture; NaF, sodium fluoride; PAEC, porcine aortic endothelial cell; PDBu, phorbol-12,13 dibotyrate; PMA, phorbol-12 myristate-13-acetate; RT, room temperature ; siRNA, small interfering RNA; SVEC4-10, SV40-transformed murine en-dothelial cell; WT, wild type

Setting up of a hospital Covid‐19 vaccination center: A descriptive study

Abstract Background and Aims The coronavirus pandemic challenged countries worldwide in a race against contaminations and variants. Vaccination campaigns were the answer to such an infectious spread. This descriptive study presents the organizational process of the setting up of a Covid‐19 vaccination center in a French University Hospital in January 2021, the issues encountered along the way and assessment of adaptability. Methods Three major stakeholders: SARS CoV‐2 crisis referent, referring vaccination medical doctor and referring vaccination pharmacist retraced key moments and identified issues encountered during the setting up of the vaccination center and its long term maintenance, threw a series of meetings. Records of crisis and periodic meetings that took place threw out the vaccination campaign were consulted. Results A multidisciplinary crisis steering committee with nine different professionals was created January 3. Logistics for the vaccination center opening were discussed: location, informatics, appointment‐scheduling, pharmaceutical circuit, internal circuit, human resources, and information communication. The vaccination center was ready to welcome healthcare workers in less than 24 h on January 4. The first month, 2757 1st shots were administered, leading up to a total of 9167 1st shots during 6 months of activity. From January to June 2021, the multidisciplinary group dealt and adapted its processes to challenging and unexpected situations. Indeed, issues encountered with Pfizer BioNTech's and AstraZeneca's vaccine, were: supply shortages, vaccine manipulation, targeted populations, pharmacovigilance, and general communication. Conclusion This descriptive study provides an exclusive insight on how a hospital vaccination center was organized and adapted during Covid‐19 pandemic to ensure healthcare workers' security and resilience, and to protect high risk patients of severe Covid‐19 infection

Discoidin domain receptor 1 controls linear invadosome formation via a Cdc42-Tuba pathway.

International audienceAccumulation of type I collagen fibrils in tumors is associated with an increased risk of metastasis. Invadosomes are F-actin structures able to degrade the extracellular matrix. We previously found that collagen I fibrils induced the formation of peculiar linear invadosomes in an unexpected integrin-independent manner. Here, we show that Discoidin Domain Receptor 1 (DDR1), a collagen receptor overexpressed in cancer, colocalizes with linear invadosomes in tumor cells and is required for their formation and matrix degradation ability. Unexpectedly, DDR1 kinase activity is not required for invadosome formation or activity, nor is Src tyrosine kinase. We show that the RhoGTPase Cdc42 is activated on collagen in a DDR1-dependent manner. Cdc42 and its specific guanine nucleotide-exchange factor (GEF), Tuba, localize to linear invadosomes, and both are required for linear invadosome formation. Finally, DDR1 depletion blocked cell invasion in a collagen gel. Altogether, our data uncover an important role for DDR1, acting through Tuba and Cdc42, in proteolysis-based cell invasion in a collagen-rich environment

Physiological type I collagen organization induces the formation of a novel class of linear invadosomes

This study shows that fibrillar collagen I is the physiological inducer of a novel class of invadosomes, which we named “linear invadosomes.” They are dependent on the scaffold protein Tks5 and are able to degrade extracellular matrix elements. Moreover, we demonstrate that they are β1- and β3-integrin independent, unlike classical invadosomes