Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Mouse bone marrow cells transfected with mmu-miR-142-3p mimic oligo.

ABSTRACT: Tumor progression is accompanied by an altered myelopoiesis that causes the accumulation of cells inhibiting anti-tumor T lymphocytes. We previously reported that immunosuppressive cells can be generated in vitro from bone marrow cells (BM) after four days GM-CSF and IL-6 treatment. Here, we describe that miR-142-3p down-regulation directs macrophage differentiation and determines the acquisition of their immunosuppressive function in cancer. Enforced miR over-expression impaired monocyte to macrophage transition both in vitro and in vivo. Conversely, forced miR down-regulation promoted the generation of immunosuppressive macrophages even during G-CSF-induced granulocytic differentiation. To identify how miR-142-3p regulates MDSC generation and activity, we analyze the gene expression of BM cultures transfected with either CTRL- or miR 142-3p mimic oligo -transfected before four days GM-CSF and IL-6 treatment. Keywords: Expression profiling by array BM cells were transfected either CTRL- or miR 142-3p mimic oligo before GM-CSF and IL-6 treatment to generate in vitro MDSCs during enforced miR over-expression. A triplicate of each sample was considered.Total RNA from obtained in vitro BM-differentiated MDSCs was isolated by Trizol reagent, and cRNA samples were hybridized to the Affymetrix GeneChip MOE430 2.0.

ORGANISM(S): Mus musculus

SUBMITTER: Stefania Bortoluzzi

PROVIDER: E-GEOD-39803 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

miR-142-3p prevents macrophage differentiation during cancer-induced myelopoiesis.

Sonda Nada N Simonato Francesca F Peranzoni Elisa E Calì Bianca B Bortoluzzi Stefania S Bisognin Andrea A Wang Ena E Marincola Francesco M FM Naldini Luigi L Gentner Bernhard B Trautwein Christian C Sackett Sara Dutton SD Zanovello Paola P Molon Barbara B Bronte Vincenzo V

Immunity 20130601 6

Tumor progression is accompanied by an altered myelopoiesis causing the accumulation of immunosuppressive cells. Here, we showed that miR-142-3p downregulation promoted macrophage differentiation and determined the acquisition of their immunosuppressive function in tumor. Tumor-released cytokines signaling through gp130, the common subunit of the interleukin-6 cytokine receptor family, induced the LAP∗ isoform of C/EBPβ transcription factor, promoting macrophage generation. miR-142-3p downregula ...[more]

PMID: 23809164

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Project description:Tumor growth is associated with a profound alteration of myelopoiesis, leading to recruitment of immunosuppressive cells known as myeloid-derived suppressor cells (MDSCs). Analyzing the cytokines affecting myelo-monocytic differentiation produced by various experimental tumors, we found that GM-CSF, G-CSF, and IL-6 allowed a rapid generation of MDSCs from precursors present in mouse and human bone marrow (BM). BM-MDSCs induced by GM-CSF+IL-6 possessed the highest tolerogenic activity, as revealed by the ability to impair the priming of IFN- -producing CD8+ T cells upon in vivo adoptive transfer. Moreover, adoptive transfer of syngeneic, GM-CSF+IL-6-conditioned MDSCs to diabetic mice transplanted with allogeneic pancreatic islets resulted in long term acceptance of the allograft and correction of the diabetic status. Cytokines inducing MDSCs acted on a common molecular pathway. Immunoregulatory activity of both tumor-induced and BM-derived MDSCs was entirely dependent on C/EBP transcription factor, a key component of the emergency myelopoiesis triggered by stress and inflammation. Adoptive transfer of tumor antigen-specific CD8+ T lymphocytes resulted in therapy of established tumors only in mice lacking C/EBP in myeloid compartment. These data unveil another link between inflammation and cancer and identify a novel molecular target to control tumor-induced immune suppression. We used gene expression analysis to identify those factors, secreted by tumor-infiltrating MDSC, which could drive emathopoiesis. Moreover we compare gene expression profile of tumor-induced MDSC, obtained from either the spleen and the tumor infiltrate of tumor bearing mice, and in vitro bone marrow-derived MDSC. CD11b+ cells were immunomagnetically enriched from various murine tissue and experimental conditions, and cRNA samples were prepared accordingly to Expression Analysis: Technical Manual. 701021 Rev. 5. Santa Clara, CA, Affymetrix; 2004, and hybridized to the Affymetrix GeneChip MOE430 2.0 array which contains more than 45,000 probe sets, representing more than 34,000 genes. CD11b+ cells obtained from the spleen of healthy BALB/c and C57BL/6 mice were used as reference sample for tumor induced CD11b+ MDSC, enriched from either the spleen and the tumor infiltrate of tumor-bearing mice. Moreover CD11b+ cells enriched from fresh bone marrow were used as reference sample for in vitro bone marrow-differentiated MDSC, obtained with either GM-CSF+IL-6 and GM-CSF+G-CSF 4 days cytokine cocktail treatment.

Dataset Information

Mouse bone marrow cells transfected with mmu-miR-142-3p mimic oligo.

Publications

miR-142-3p prevents macrophage differentiation during cancer-induced myelopoiesis.

Similar Datasets

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