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Global gene expression profiling in mouse plasma cell tumor precursor and bystander cells revels potential intervention targets for plasma-cell neoplasia

ABSTRACT: We extracted nascent plasma cell tumor (PCT) cells from within inflammatory granulomas (OG) isolated from intraperitoneal pristane-injected BALB/c.iMyc Eμ mice at five different time points during tumor progression. We used laser capture micro-dissection to collect incipient PCT cells and analyzed their global gene expression on Affymetrix Mouse Genome 430A microarrays. Two independent studies were performed with different sets of mice

ORGANISM(S): Mus musculus

PROVIDER: GSE34078 | GEO | 2011/12/02

SECONDARY ACCESSION(S): PRJNA150005

REPOSITORIES: GEO

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Global gene expression profiling in mouse plasma cell tumor precursor and bystander cells revels potential intervention targets for plasma-cell neoplasia

Project description:We extracted nascent plasma cell tumor (PCT) cells from within inflammatory granulomas (OG) isolated from intraperitoneal pristane-injected BALB/c.iMyc Eμ mice at five different time points during tumor progression. We used laser capture micro-dissection to collect incipient PCT cells and analyzed their global gene expression on Affymetrix Mouse Genome 430A microarrays. Two independent studies were performed with different sets of mice RNA was extracted from both laser capture samples and whole tissue sections at 5 different times after tumor initiation: 7 days, 17 days, 33 days, 49/46 days and 104/105 days in two independent experiments, studies 1 and 2

2011-12-02 | E-GEOD-34078 | biostudies-arrayexpress

Global gene expression profiling in mouse plasma cell tumor precursor and bystander cells reveals potential intervention targets for plasma cell neoplasia.

Project description:Tumor progression usually proceeds through several sequential stages, any of which could be targets for interrupting the progression process if one understood these steps at the molecular level. We extracted nascent plasma cell tumor (PCT) cells from within inflammatory oil granulomas (OG) isolated from IP pristane-injected BALB/c.iMyc(E?) mice at 5 different time points during tumor progression. We used laser capture microdissection to collect incipient PCT cells and analyzed their global gene expression on Affymetrix Mouse Genome 430A microarrays. Two independent studies were performed with different sets of mice. Analysis of the expression data used ANOVA and Bayesian estimation of temporal regulation. Genetic pathway analysis was performed using MetaCore (GeneGo) and IPA (Ingenuity). The gene expression profiles of PCT samples and those of undissected OG samples from adjacent sections showed that different genes and pathways were mobilized in the tumor cells during tumor progression, compared with their stroma. Our analysis implicated several genetic pathways in PCT progression, including biphasic (up- and then down-regulation) of the Spp1/osteopontin-dependent network and up-regulation of mRNA translation/protein synthesis. The latter led to a biologic validation study that showed that the AMPK-activating diabetes drug, metformin, was a potent specific PCT inhibitor in vitro.

| S-EPMC3271714 | biostudies-literature

Genome-wide expression analysis of mouse plasma cell tumors show importance of IL-6 in tumor development

Project description:Interleukin 6 (IL-6) is a pro-inflammatory cytokine important for plasmacytomagenesis. Here we showed that the strom cell-derived IL-6 is critical for plasma cell tumors (PCTs). The gene expression analysis of mouse PCTs showed that adoptive-transfer PCT and spontaneous PCT have similar patterns. Further, the mouse tumors also illustrated resemblance to human multiple myeloma (MM).

2015-07-27 | GSE60282 | GEO

CAFs are activated in incipient neoplasia to orchestrate tumor promoting inflammation in an NF-κB-dependent manner.

Project description:Full title: Cancer Associated Fibroblasts are activated in incipient neoplasia to orchestrate tumor promoting inflammation in an NF-κB-dependent manner. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation, and invasion. We demonstrate that CAFs also mediate tumor-enhancing inflammation. Using a mouse model of squamous skin cancer, we found a pro-inflammatory gene signature in CAFs isolated from dysplastic skin. This signature was also evident in CAFs from skin as well as mammary and pancreatic tumors in mice, and in human cancer. Surprisingly, the inflammatory signature was already activated in CAFs isolated from the incipient hyperplastic stage in multistep tumorigenesis. CAFs from this pathway functioned to promote macrophage recruitment, neovascularization and tumor growth in vivo, activities abolished when NF-κB signaling was inhibited. Additionally, we show that normal dermal fibroblasts can be “educated” by carcinoma cells to express pro-inflammatory genes.

2009-09-02 | GSE17817 | GEO

Mus musculus

Project description:PCT and normal

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ABHD11 maintains 2-oxoglutarate metabolism by preserving functional lipoylation of the 2-oxoglutarate dehydrogenase complex

Project description:2-oxoglutarate (2-OG or α-ketoglutarate) relates mitochondrial metabolism to cell function by modulating the activity of 2-OG dependent dioxygenases involved in the hypoxia response and DNA/histone modifications. However, metabolic pathways that regulate these oxygen and 2-OG sensitive enzymes remain poorly understood. Here, using CRISPR Cas9 genome-wide utagenesis to screen for genetic determinants of 2-OG levels, we uncover a redox sensitive mitochondrial lipoylation pathway, dependent on the mitochondrial hydrolase ABHD11, that signals changes in mitochondrial 2-OG metabolism to 2-OG dependent dioxygenase function. ABHD11 loss or inhibition drives a rapid increase in 2-OG levels by impairing lipoylation of the 2-OG dehydrogenase complex (OGDHc) – the rate limiting step for mitochondrial 2-OG metabolism. Rather than facilitating lipoate conjugation, ABHD11 associates with the OGDHc and maintains catalytic activity of lipoyl domain by preventing the formation of lipoyl adducts, highlighting ABHD11 as a regulator of functional lipoylation and 2-OG metabolism.

2020-07-27 | PXD020128 | Pride

Transcription profiling of inguinal lymph nodes from rats injected with pristane, phytol, both pristane and phytol or untreated to obtain a molecular understanding of the protective effects of phytol on pristane induced arthritis

Project description:Comparison of gene expression in inguinal lymph nodes in four groups of rats; one with induced arthritis by injection with pristane, one injected with phytol, one injected with both pristane and phytol, and one untreated group. The objective was to obtain a molecular understanding of the protective effects of phytol on pristane induced arthritis (PIA). The animals were sacrificed close to disease onset, i.e. ten days after administration.

2007-12-31 | E-MEXP-782 | biostudies-arrayexpress

rDNA chromatin interactions in the MYC-driven Eμ-Myc transgenic mouse model of B-cell lymphoma [4C-seq]

Project description:Long-range interactions of ribososomal DNA (rDNA) identified by 4C-seq in mouse wildtype, premalignant and malignant Eμ-Myc cells and tissue culture adapated Eμ-Myc-shUbtf and Eμ-Myc-LMP (empty vector) cells.

2019-02-06 | GSE70221 | GEO

Maladaptive upregulation of aminoprocalcitonin fuels seizure self-sustaining by boosting energy supply in refractory status epilepticus

Project description:To investigate the biological functions of aminoprocalcitonin (NPCT) and its parent peptide procalcitonin (PCT) in neurons, we stimulated rat primary hippocampal neurons at DIV7 with 1 nM NPCT and 1 nM PCT for 24 h, respectively. Alterations in transcriptomes were analyzed with RNA-seq.

2023-05-10 | GSE217955 | GEO

Integrated cellular and plasma proteomics reveals common and systemic signatures in contrasting B-cell cancers

Project description:Approximately 800,000 leukaemia and lymphoma cases are diagnosed worldwide each year. Burkitt’s lymphoma and chronic lymphocytic leukaemia represent contrasting examples of B-cell cancers, modelled by Eμ-myc and Eμ-TCL1 mice, respectively. To better understand B-cell cancers and systemic effects of oncogenesis, tumours and plasma from these models were profiled by mass spectrometry proteomics. 8270 cellular and 2095 plasma proteins were fully quantitated by isobaric labelling, of which 695 and 279 demonstrated overabundance coinciding in both tumour models, respectively. Co-occurring upregulated cellular tumour processes included ribosome biogenesis, translation, cell cycle promotion and chromosome segregation. Tumour plasma overabundance highlighted immunity, inflammation, microenvironment interactions, a prolific tumour lysis signature and putative biomarkers of early-stage cancer. Integrative evaluation of tumours and plasma provided systemic insight not captured in isolation. Overall, these findings provide a detailed characterisation of systemic oncogenesis in two contrasting B-cell tumour models, identifying extensive common profiles in both tumour cells and plasma.

2017-01-10 | PXD004608 | Pride

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