Project description:Neutrophils are the most abundant circulating leucocytes and constitute an essential component of innate immunity. Although their role in cancer development is still poorly defined, pro- or anti-tumor properties have been attributed to tumor-associated neutrophils (TANs), suggesting major functional diversities. In this study, we focused on the mechanisms involved in neutrophil accumulation within the lung tumor mass. We first identified G-CSF as an inducer of the high-affinity glucose transporter Glut1 in neutrophils, increasing their survival ex vivo. In a genetically engineered mouse model of lung adenocarcinoma, we report that TANs have an increased Glut1 expression and glucose metabolism compared to normal neutrophils. To elucidate the impact of glucose uptake on TANs, we used an in vivo strategy based on two recombinases, Flp to initiate lung tumors, and Cre to delete Glut1 specifically in neutrophils. We demonstrate that the loss of Glut1 decreases the SiglecFhigh TAN subpopulation by accelerating neutrophil turnover in tumors through reduced survival and augmented recruitment. Accelerated TAN turnover led to a decreased tumor growth and synergized with radiotherapy. Altogether, our results demonstrate the importance of Glut1 for neutrophil turnover, which directly affects the pro- versus anti-tumor balance within the tumor. These results also suggest that metabolic vulnerabilities can be exploited to target tumor-supportive neutrophil populations.
Project description:Side population (SP) cells are highly enriched in stem and progenitor cells. CD45+and CD45- SP cells were found at all developmental lung stages with the highest frequency of cells present at embryonic day 17.5 (E17.5), In order to clarify the role of these cells in lung development, we used oligonucleotide microarrays to evaluate their gene expression profiles. To do this, oligonucleotide gene arrays were performed in triplicate on RNA derived from CD45+ and CD45-SP cells, and CD45+ and CD45- non-SP populations (main population; MP) isolated from the E17.5 lung.
Project description:Side population (SP) cells are highly enriched in stem and progenitor cells. CD45+and CD45- SP cells were found at all developmental lung stages with the highest frequency of cells present at embryonic day 17.5 (E17.5), In order to clarify the role of these cells in lung development, we used oligonucleotide microarrays to evaluate their gene expression profiles. To do this, oligonucleotide gene arrays were performed in triplicate on RNA derived from CD45+ and CD45-SP cells, and CD45+ and CD45- non-SP populations (main population; MP) isolated from the E17.5 lung. Keywords: parallel sample
Project description:Comparative gene expression profiling analysis of RNA-seq data in CD45- lung tumor cells from tumor-burdened lungs of KrasLSL-G12D/+Tp53fl/fl and KrasLSL-G12D/+Tp53fl/flUsp25-/- mice 10 weeks after they were intranasally injected with Ad-Cre.
Project description:Comparative gene expression profiling analysis of RNA-seq data in CD45- lung tumor cells from tumor-burdened lungs of KrasLSL-G12D/+Lkb1fl/fl and KrasLSL-G12D/+Lkb1fl/flUsp25-/- mice 10 weeks after they were intranasally injected with Ad-Cre.
Project description:To understand if cancer cells that metastasize to the lung induce changes of gene expression in associated endothelial cells to promote metastatic growth, we profiled the gene expression of CD31+/CD45- cells sorted from unchallenged normal mouse lungs and dissected metastatic nodules.
Project description:Exploration of proteome differences between CD45+ and CD45- cell types in renal cell carcinoma tumors and normal adjacent tissue patient samples.
Project description:Analysis of gene induced upon infection by MV in cocultures of tumor cells (CD45-) and myeloid cells (CD45+). The hypothesis tested in the present study was that MV induce innate immune response in tumor cells and myeloid cells cocultured together.