A Comprehensive Proteomics Analysis Reveals Dynamic Phenotypes of Tumor-associated Macrophages and Their Precursor Cells in Tumor Progression
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus Musculus
SUBMITTER: 
Jian Wang
PROVIDER: PXD046492 | iProX | Mon Oct 30 00:00:00 GMT 2023
REPOSITORIES: iProX
Similar Datasets
Project description:The gene expression profile of TAMs sorted from vehicle control tumors in GIST mice (Sommer et al, PNAS 2003) was compared to TAMs sorted from mice after 2 weeks of imatinib therapy The Affymetrix Mouse Genome 430A 2.0 platform was used Each treatment group had 8 mice. After 2 weeks of treatment, mice were sacrificed and tumors digested with collagenase. TAMs were then FACS sorted and pooled by group. Pooled groups were run in duplicate for the gene expression array.
2013-11-20 | E-GEOD-51698 | biostudies-arrayexpress
Project description:Clinical and experimental evidence indicates that tumor-associated macrophages (TAMs) promote malignant progression. In breast cancer, TAMs enhance tumor angiogenesis, tumor cell invasion, matrix remodeling, and immune suppression against the tumor. In this study, we examined late-stage mammary tumors from a transgenic mouse model of breast cancer. We used flow cytometry under conditions that minimized gene expression changes to isolate a rigorously defined TAM population previously shown to be associated with invasive carcinoma cells. The gene expression signature of this population was compared with a similar population derived from spleens of non-tumor-bearing mice using high-density oligonucleotide arrays. Using stringent selection criteria, transcript abundance of 460 genes was shown to be differentially regulated between the two populations. Bioinformatic analyses of known functions of these genes indicated that formerly ascribed TAM functions, including suppression of immune activation and matrix remodeling, as well as multiple mediators of tumor angiogenesis, were elevated in TAMs. Further bioinformatic analyses confirmed that a pure and valid TAM gene expression signature in mouse tumors could be used to assess expression of TAMs in human breast cancer. The data derived from these more physiologically relevant autochthonous tumors compared with previous studies in tumor xenografts suggest tactics by which TAMs may regulate tumor angiogenesis and thus provide a basis for exploring other transcriptional mediators of TAM trophic functions within the tumor microenvironment. Tumor-associated macrophages from late-stage mouse mammary tumors compared to splenic macrophages from non-tumor-bearing littermate controls. 4 biological replicates of each population were compared via gene expression arrays.
2010-06-21 | E-GEOD-18404 | biostudies-arrayexpress
Project description:The gene expression profile of TAMs sorted from vehicle control tumors in GIST mice (Sommer et al, PNAS 2003) was compared to TAMs sorted from mice after 2 weeks of imatinib therapy The Affymetrix Mouse Genome 430A 2.0 platform was used
2013-11-20 | GSE51698 | GEO
Project description:Tumor associated macrophages show signs of both, classical pro-inflammatory as well as alternative macrophage activation. The aim of this study was to compare TAMs across tumor types, to characterize their phenotype in detail and to identify the signaling nodules involved regulating classical and alternative activation traits. To identify gene expression profiles and pathways differentially activated in tumor-associated macrophages (TAMs) we isolated TAMs from in vivo animal models of EG7 thymoma (n=3), glioma (n=3) and neuroblastoma (n=3) by tumor digestion and subsequent enrichment of CD11b+ cells using Miltenyi magnetic beads. Thymomas grown in WT or Myd88-/- mice (n=5 per group) were used to identify TLR/IL1R dependent signaling in TAMs. RNA extracted from CD11b+ TAMs was analyzed using the Affymetrx HT_MG-430_PM arrays. For in-depth analysis of the role of inflammatory signaling by TNFR1 (Tnfrsf1a) and/or Myd88, EG7 TAM populations A (CD11b+, Ly6G-, Ly6C+, MHCII-) and C (CD11b+, Ly6C-, MHCII+) were isolated by flow cytometric sorting from WT, TNFR1-/-, Myd88flox/flox; Tie2-Cre and TNFR-/-; Myd88flox/flox; Tie2-cre mice and extracted RNA was analyzed by microarray using the Mouse Gene 2.0 GeneChip arrays (n=2 per genotype and population).
2015-04-28 | E-GEOD-59047 | biostudies-arrayexpress
Project description:To investigate the effects of OMVs and IN@OMVs treatments on mouse tumor-associated macrophages, mouse tumors were harvested after treatment, and CD11b+ F4/80+ labeled cells (TAMs) were sorted by FACS for RNA sequencing.
2025-07-23 | GSE285523 | GEO
Project description:Macrophages have been implicated in breast cancer progression and metastasis, but relatively little is known about the genes and pathways that are involved. Using a conditional allele of Ets2 in the mouse, we have identified Ets2 as a critical gene in tumor associated macrophages (TAMs) that specifically promotes mammary tumor metastasis. Loss of Ets2 in TAMs decreased the frequency and size of lung metastases without impacting primary tumor burden. Expression profiling of isolated tumor macrophages established that Ets2 deficiency resulted in the de-repression of a defined set of anti-angiogenic genes. Activation of this transcriptional program correlated with decreased angiogenesis in metastatic tumors and decreased metastatic growth. Comparison of this Ets2-specific TAM expression profile with human breast cancer profiles revealed a macrophage gene expression signature that could predict overall survival of estrogen receptor negative patients. In summary, we have identified a critical factor, Ets2, in TAMs that represses a transcriptional program to promote the growth of mammary tumor metastases in the lung. Breast TAMs were isolated from early-stage PyMT-induced mammary tumors expressing Ets2 and also from the tumors with Ets2-deficient TAMs. Since macrophages have also been implicated in normal mammary gland remodeling, normal remeodeling macrophages were also purified from females expressing Ets2 and the ones where Ets2 is deleted in the macrophages. One RNA sample was extracted from each genetic group for gene-expression profiling.
2010-01-05 | E-GEOD-12863 | biostudies-arrayexpress
Project description:To better understand the impact of integrin beta3 signaling in myeloid cells on the tumor microenvironment, we compared the gene expression profiles of FACS isolated GFP+ PyMT-BO1 MFP tumor cells and also M2 TAMs (CD11b+Gr1-F4/80+CD206+) from tumor tissue of WT mice and b3ÎÎÎ mice. PyMT-BO1-GFP-Luc tumor cells (100,000) were injected into mammary fat pad (MFP) tissue from WT and b3KOM mice. PyMT-BO1-GFP-Luc cells and CD206hi tumor-associated macrophages (TAMs) were FACS-sorted from day 10 MFP tumor tissue. FACS-sorted cells directly used for RNA extraction and hybridization on Affymetrix microarrays.
2015-12-11 | E-GEOD-75882 | biostudies-arrayexpress
Project description:Metastasis is the primary cause of mortality in breast cancer patients. Tumor associated macrophages (TAMs) are active collaborators in mediating several steps of the tumor metastatic cascade, but the molecular details governing this collaboration remain ill-defined. Colony Stimulating Factor 1 (CSF1), a factor critical for macrophage differentiation and survival, functions to recruit TAMs to the primary tumor site, and anti-CSF1 therapies are in clinical trials.In this study, we tested the effect of inhibiting CSF1 signaling in macrophages on gene expression in metastatic tumor cells in mouse models of breast cancer metastasis. Tumor cells were sorted from lung metastases from control and CSF1R inhibitor treated mice. Several pro-tumor processes were significantly affected by CSF1R inhibitor treatment, including angiogenesis and tumor cell proliferation. In addition, a 29 gene signature derived from this data could retrospectively predict survival in a cohort of luminal B breast cancer patients. Collectievly, our results highlight the utility of employing CSF1R inhibitors for the treatment of metastatic breast cancer. GFP tagged MVT1 metastatic mammary tumor cells were injected intravenously into FVB/N mice. Mice were gavaged with the CSF1R inhibitor GW2580 or vehicle starting one week post injection. GFP tagged tumor cells were sorted from metastatic tumor bearing lungs 1 and 2 weeks post injection from 2 vehicle treated mice for each. These are denoted 1_week_WT and 2_week_WT respectively. GFP tagged tumor cells were simultaneously sorted from mice gavaged with GW2580. These samples are denoted 2_week_GW. RNA was extracted and gene expression profiling was performed using the Affymetrix Mouse Genome 430 2.0 Array platform.
2014-03-13 | E-GEOD-55855 | biostudies-arrayexpress
Project description:Tumor-associated macrophages (TAMs) have immunosuppressive capacity in mouse models of cancer. Here we show that the genetic deletion of the microRNA (miRNA)-processing enzyme DICER in TAMs broadly programs them to a CD11c+MRC1â/low M1-like immunostimulatory phenotype characterized by activated interferon-γ (IFN-γ)/STAT1/IRF signaling. M1-like TAM programming fostered the recruitment of cytotoxic T-cells (CTLs), including tumor-antigen-specific CTLs, inhibited tumor growth, and enhanced the efficacy of PD1 checkpoint blockade. Bioinformatics analysis of TAM transcriptomes identified a limited set of miRNAs putatively involved in TAM programming. Re-expression of Let-7 in Dicer-deficient TAMs was sufficient to partly rescue the M2-like (protumoral) TAM phenotype and abate tumor CTL infiltration. Targeted suppression of DICER activity in TAMs may, therefore, stimulate antitumor immunity and enhance the efficacy of cancer immunotherapy. To explore the role of DICER in the development, activation and immunological functions of TAMs, we crossed homozygous LysM-Cre (Clausen et al., 1999) with Dicerlox/lox (Harfe et al., 2005) mice to obtain mice with myeloid-cell-specific Dicer1 gene deletion (LysM-Cre;Dicerâ/â, referred to as Dâ/â). These mice were then backcrossed to LysM-Cre to obtain the control LysM-Cre; Dicer+/+ mice (referred to as D+/+). Both LysM-Cre and Dicerlox/lox mutations were always homozygous in our experiment. We then inoculated Lewis lung carcinoma (LLC) cells subcutaneously (s.c.) in Dâ/â and control D+/+ mice. Once the tumors were established, we isolated by fluorescence-activated cell sorting (FACS) tumor-associated macrophages (F4/80+ cells).
2016-06-13 | E-GEOD-76356 | biostudies-arrayexpress
Project description:CD200 is overexpressed in human solid tumors such as neuroblastoma and melanoma and considered to be a checkpoint molecule to be targeted for cancer immunotherapy. However, its role in tumor microenvironment (TME) is not well understood. In this study, we evaluated the role of CD200-CD200R pathway in TME using two human relevant, CD200-positive murine tumor models, i.e. the mouse neuroblastoma NB9464D, and melanoma Yummer1.7 models. We found that in CD200R-/- mice, both tumor types grew significantly slower than in wild type mice. TME analyses using scRNAseq and flow cytometry revealed that tumors from CD200R-/- mice overall recruited more CD45+ immune cells including CD4+ and CD8+ T cells and NK cells but less neutrophils into tumors. Antibody depletion experiments revealed that immune effectors including CD4+ and CD8+ T cells, and NK cells are crucial in inhibiting tumor growth in CD200R-/- mice. Mechanistically, we found that CD200R signaling differentially regulates the expression of chemokines in TAMs. In the absence of CD200R, TAMs upregulate CCL24 and CCL8 and downregulate CXCL3, CXCL2 and CCL3 via activation of Erk and/or P38 MAP kinases. Increased expression of CCL24 in TAMs resulted in increased recruitment of eosinophils, which contributes to anti-tumor activity. Thus, CD200R signaling regulates myeloid cell production of chemokines in TME, which explains the differential recruitment of immune effectors and downregulation of neutrophils.
2023-05-30 | GSE211963 | GEO