Macrophages represent an important component of the tumor microenvironment and play a complex role in cancer progression. These cells are characterized by a high degree of plasticity, and alter their phenotype in response to local environmental cues. While the M1/M2 classification of macrophages has been widely used, the complexity of macrophage phenotypes specifically in lung cancer has not been well studied. In this study we employed an orthotopic immunocompetent model of lung adenocarcinoma in which murine lung cancer cells are directly implanted into the left lobe of syngeneic mice. Using multi-marker flow cytometry we defined and recovered several distinct populations of monocytes/macrophages from tumors at different stages of progression. We used RNA-seq transcriptional profiling to define distinct features of each population and determine how they change during tumor progression. We defined an alveolar resident macrophage population that does not change in number and express multiple genes related to lipid metabolism and lipid signaling. We also defined a population of tumor-associated macrophages that increase dramatically with tumor, and selectively express a panel of chemokines genes. A third population, which resembles tumor-associated monocytes, expresses a large number of genes involved in matrix remodeling. By correlating transcriptional profiles with clinically prognostic genes, we show that specific monocyte/macrophage populations are enriched in genes that predict good or poor outcome in lung adenocarcinoma, implicating these subpopulations as critical determinants of patient survival. Our data underscore the complexity of monocytes/macrophages in the tumor microenvironment, and suggest that distinct populations play specific roles in tumor progression. Overall design: mRNA profiles of macrophage/monocyte cells isolated from murine control or tumor-bearing lung. From naive mice: MacA cells (MacA-N), MacB1 cells (MacB1-N), MacB2 cells (MacB2-N); from 2 week tumor bearing mice: MacA cells (MacA-2wk), MacB2 cells (MacB2-2wk), MacB3 cells (MacB3-3wk); from 3-week tumor bearing mice: MacB2 (MacB2-3wk), MacB3 cells (MacB3-3wk). Each population was analyzed in triplicate (cells were isolated in 3 independent experiments).
Expression Profiling of Macrophages Reveals Multiple Populations with Distinct Biological Roles in an Immunocompetent Orthotopic Model of Lung Cancer.
Cell line, Subject
View SamplesHuman solid tumors contain rare cancer side population (SP) cells, which expel the fluorescencent dye H33342 and display cancer stem cell characteristics. Transcriptional profiling of cancer SP cells isolated by H33342 fluorescence analysis is a newly emerging approach to discover cancer stem cell markers and aberrant differentiation pathways. Using Affymetrix expression microarrays this study investigated differential gene expression between SP and non-SP (NSP) cells isolated from the CAL-51 human mammary carcinoma cell line.
Down-regulation of the fetal stem cell factor SOX17 by H33342: a mechanism responsible for differential gene expression in breast cancer side population cells.
Specimen part
View SamplesNeuroprotective therapies for retinal degeneration may be used to rescue retinal cells and preserve vision. Hypoxic preconditioning stabilizes the transcription factor HIF-1 in the retina and strongly protects photoreceptors in an animal model of light-induced retinal degeneration.
Analysis of the retinal gene expression profile after hypoxic preconditioning identifies candidate genes for neuroprotection.
No sample metadata fields
View SamplesMorphogenesis of the mammary gland relies on the precise developmental control of morphological elements including TEBs, ducts and lobules. In the peripubertal mammary gland, rising levels of ovarian hormones control this development through a tightly controlled genetic program where specific sets of genes are up-regulated.
In utero and lactational exposure to vinclozolin and genistein induces genomic changes in the rat mammary gland.
Specimen part, Treatment
View SamplesPeripheral blood neutrophils were isolated from septic patients and treated in vitro with LPS or HMGB1
HMGB1 and LPS induce distinct patterns of gene expression and activation in neutrophils from patients with sepsis-induced acute lung injury.
No sample metadata fields
View SamplesWe developed a computational framework that integrates chromosomal copy number and gene expression data for detecting aberrations that promote cancer progression. We demonstrate the utility of this framework using a melanoma dataset. Our analysis correctly identified known drivers of melanoma and predicted multiple novel tumor dependencies. Two dependencies, TBC1D16 and RAB27A, confirmed empirically, suggest that abnormal regulation of protein trafficking contributes to proliferation in melanoma. Together, these results demonstrate the ability of integrative Bayesian approaches to identify novel candidate drivers with biological, and possibly therapeutic, importance in cancer.
An integrated approach to uncover drivers of cancer.
Cell line
View SamplesVascular endothelial growth factor is a multifunctional cytokine playing important roles in angiogenesis, tumor progression and metastasis. Alternative splicing results in the production of several different isoforms of VEGF. We have previously generated human breast cancer cells overexpressing VEGF165 or VEGF189 isoforms (referred to as the V165 and V189 clones, respectively) and showed that VEGF189-transfected cells were less tumorigenic. In this study, we used bioluminescence imaging to analyze the metastasis capacity of breast cancer cell lines (MDA-MB-321) overexpressing VEGF isoforms in nude mice. V165, V189 and control cV clones were transfected with a luciferase plasmid to generate bioluminescent clones (the V165-B, V189-B and cV clones, respectively). These clones were then injected into the left heart ventricle of nude mice.
MDA-MB-231 breast cancer cells overexpressing single VEGF isoforms display distinct colonisation characteristics.
No sample metadata fields
View SamplesThree different cell populations (6 healthy B-lymphocytes, 6 leukemic CLL B-lymphocyte of indolent form and 5 leukemic CLL B-lymphocyte of aggressive form) were stimulated in vitro with an anti-IgM antibody, activating the B-cell receptor (BCR). We analyzed the gene expression at 4 time points (60, 90, 210 and 390 minutes). Each gene expression measurement is performed both in stimulated cells and in control unstimulated cells.
Reverse-engineering the genetic circuitry of a cancer cell with predicted intervention in chronic lymphocytic leukemia.
Specimen part
View SamplesIn the context of T1 Diabetes, pro-inflammatory cytokines IL-1 and IFN- are known to contribute to -cell apoptosis;
Temporal profiling of cytokine-induced genes in pancreatic β-cells by meta-analysis and network inference.
Specimen part, Treatment, Time
View SamplesIn the context of T1 Diabetes, pro-inflammatory cytokines IL-1 and IFN- are known to contribute to -cell apoptosis;
Temporal profiling of cytokine-induced genes in pancreatic β-cells by meta-analysis and network inference.
Cell line, Treatment, Time
View Samples