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MicroRNA profiling of brain metastasis competent cell-derived exosomes

ABSTRACT: Objective of this work was to characterize the miRNA profile of exosomes isolated from brain-homing cell lines (MDA-MB-231BR, CTC1BMSM, and 70W) with their respective parental non-brain metastatic cell lines (MDA-MB-231P, CTC1P and MeWo). Exosomes derived from the six cell lines were isolated. Brain metastatic cell-derived exosomal miRNAs were compared with non brain metastatic cell lines (MDA-MB-231BR versus MDA-MB-231P, CTC1BMSM versus CTC1P, and 70W versus MeWo).

ORGANISM(S): Homo sapiens

SUBMITTER: Laura Camacho

PROVIDER: E-GEOD-48934 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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MicroRNA and protein profiling of brain metastasis competent cell-derived exosomes.

Camacho Laura L Guerrero Paola P Marchetti Dario D

PloS one 20130916 9

Exosomes are small membrane vesicles released by most cell types including tumor cells. The intercellular exchange of proteins and genetic material via exosomes is a potentially effective approach for cell-to-cell communication and it may perform multiple functions aiding to tumor survival and metastasis. We investigated microRNA and protein profiles of brain metastatic (BM) versus non-brain metastatic (non-BM) cell-derived exosomes. We studied the cargo of exosomes isolated from brain-tropic 70 ...[more]

PMID: 24066071

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MicroRNA profiling of brain metastasis competent cell-derived exosomes

Project description:Objective of this work was to characterize the miRNA profile of exosomes isolated from brain-homing cell lines (MDA-MB-231BR, CTC1BMSM, and 70W) with their respective parental non-brain metastatic cell lines (MDA-MB-231P, CTC1P and MeWo).

2013-07-16 | GSE48934 | GEO

The murine metastatic microenvironment of experimental brain metastases in breast cancer differs by host age in vivo: A proteomic study.

Project description:Breast cancer in young patients is known to exhibit more aggressive biological behavior and is associated with a less favorable prognosis than the same disease in older patients, owing in part to an increased incidence of brain metastases, the mechanistic explanations behind which remain poorly understood. We recently reported that young mice, compared to older mice, showed about a three-fold increase in the development of brain metastases in mouse models of triple-negative and luminal B breast cancer. Here we have performed a quantitative mass spectrometry-based proteomic analysis to identify proteins contributing to age-related disparities in the development of breast cancer brain metastases. Using a mouse model of brain-tropic (MDA-MB-231BR) triple-negative breast cancer, we harvested subpopulations of tumor metastases, the tumor-adjacent metastatic microenvironment, and uninvolved brain tissues via laser microdissection followed by quantitative proteomic analysis using high resolution mass spectrometry to characterize differentially abundant proteins contributing to age-dependent rates of brain metastasis.

2024-01-11 | PXD042346 | Pride

Deep sequencing of exosomal and cellular miRNAs in MDA-MB-231 and MCF-10A cells

Project description:To identify the miRNAs that are differentially expressed and secreted between the MDA-MB-231 metastatic breast cancer cells and the MCF-10A non-cancerous human mammary epithelial cells, we profiled the cellular and exosomal small RNAs (between 17 and 52 nt) isolated from these two cell lines by Solexa deep sequencing. MiRNAs that are significantly different between the two cell lines are identified. RNA was extracted from cultured MDA-MB-231 and MCF-10A cells or purified exosomes secreted by these cells, and subjected to library construction and Solexa deep sequencing.

2013-09-01 | E-GEOD-50429 | biostudies-arrayexpress

Analyses of Human Brain Metastases of Breast Cancer Reveal the Association between HK2 Up-Regulation and Poor Prognosis

Project description:Analyses of Resected Human Brain Metastases of Breast Cancer Reveal the Association between Up-Regulation of Hexokinase 2 and Poor Prognosis. Brain metastases of breast cancer seem to be increasing in incidence as systemic therapy improves. Metastatic disease in the brain is associated with high morbidity and mortality. We present the first gene expression analysis of laser-captured epithelial cells from resected human brain metastases of breast cancer compared with unlinked primary breast tumors. The tumors were matched for histology, tumor-node-metastasis (TNM) stage, and hormone receptor status. Most differentially expressed genes were down-regulated in the brain metastases, which included, surprisingly, many genes associated with metastasis. Quantitative real-time PCR analysis confirmed statistically significant differences or strong trends in the expression of six genes: BMP1, PEDF, LAMγ3, SIAH, STHMN3, and TSPD2. Hexokinase 2 (HK2) was also of interest because of its increased expression in brain metastases. HK2 is important in glucose metabolism and apoptosis. In agreement with our microarray results, HK2 levels (both mRNA and protein) were elevated in a brain metastatic derivative (231-BR) of the human breast carcinoma cell line MDA-MB-231 relative to the parental cell line (231-P) in vitro. Knockdown of HK2 expression in 231-BR cells using short hairpin RNA reduced cell proliferation when cultures were maintained in glucose-limiting conditions. Finally, HK2 expression was analyzed in a cohort of 123 resected brain metastases of breast cancer. High HK2 expression was significantly associated with poor patient survival after craniotomy (P = 0.028). The data suggest that HK2 overexpression is associated with metastasis to the brain in breast cancer and it may be a therapeutic target. Common reference design, disease state design.

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2019-03-01 | GSE111504 | GEO

Gene expression profile in breast cancer cells

Project description:We report the gene expression patterns in MDA-MB-231 (a line selected for low metastatic ability), MDA-MB-231-1833 (its bone-tropic metastatic derivative line), MDA-MB-231p27CK-DD (a phosphomimetic cell line), MDA-MB-231-1833shp27 (p27 knockdown cell line), MDA-MB-231-1833PF1502 (PI3K inhibitor treatment). It shows that the gene expression pattern are regulated in a p27 phosphorylation-dependent manner.

2019-03-19 | GSE112445 | GEO

Identification of LncRNA Expression Signatures for breast cancer brain metastasis (BCBM)

Project description:To identify BCBM-relevant lncRNAs, we assessed the expression profiles of lncRNAs in parental MDA-MB-231 (231-PAR) cells and isogenic brain metastatic cells (231-BRN), which were isolated from brain-seeking 231-PAR cells

2017-03-01 | GSE79540 | GEO

MicroRNA profile of cells and exosomes

Project description:The goal of this study is to report that breast cancer associated exosomes contain microRNAs (miRNAs) associated with the RISC Loading Complex (RLC) and display cell-independent capacity to process precursor microRNAs (pre-miRNAs) into mature miRNAs. Pre-miRNAs, along with Dicer, AGO2, and TRBP, are present in exosomes of cancer cells. CD43 mediates the accumulation of Dicer specifically in cancer exosomes. Cancer exosomes mediate an efficient and rapid silencing of mRNAs to reprogram the target cell transcriptome. Exosomes derived from cells and sera of patients with breast cancer instigate non-tumorigenic epithelial cells to form tumors in a Dicer-dependent manner. These findings offer opportunities for the development of exosomes based biomarkers and therapies. Exosomes from cancer cells and non-tumorigenic cells were isolated using established ultracentrifugation methods. The global miRNA content of cancer exosomes and normosomes was investigated. Profiling of cells themselves was also used as a control. Exosomes with Dicer down regulation (MCF10AshDicer and MDA-MB-231shDicer exosomes), as well as MDA-MB-231 exosomes that contain a Dicer antibody inside were used to study the function Dicer protein in the microRNA biogenesis in exosomes.

2014-08-27 | E-GEOD-60714 | biostudies-arrayexpress

LncRNA Uc003xsl.1 Activates of NF-κB/IL8 Axis to Promotes Triple-negative Breast Cancer Progression via A Decoy Role to NKRF [lnc231]

Project description:To discover the potential drivers of TNBC metastasis, we established an in vivo model by injecting MDA-MB-231cells into the tail veins of mice. Then, the breast tumor cells that successfully grew into metastatic lung tumors were collected and expanded in vitro, followed by re-injected into the tail veins of mice for lung metastasis. After three rounds of selection, a highly metastatic subline, MDA-MB-231-P3, was established, and more frequent micro-metastasis was detected in MDA-MB-231-P3 groups than that of MDA-MB-231 groups when the lungs of mice were stained with hematoxylin and eosin (HE). The lncRNA profiles of MDA-MB-231 or MDA-MB-231-P3 cells were analyzed by lncRNA sequencing. A total of 267 lncRNAs in MDA-MB-231-P3 cells were upregulated more than 2-fold in comparison to the MDA-MB-231 cells.

2021-11-29 | GSE163900 | GEO

Transcription profiling of human breast cancer metastasis to the brain to identify genes involved

Project description:Brain metastasis is one of the most feared complications of cancer and the most common intracranial malignancy in adults. Its underlying mechanisms remain unknown. From breast cancer patients with metastatic disease we isolated cell populations that aggressively colonize the brain. Transcriptomic analysis of these cells yielded overlapping gene sets whose expression is selectively associated with brain metastasis. The expression of seventeen of these genes in primary breast tumors is associated with brain relapse in breast cancer patients. Some of these genes are also associated with metastasis to lung but not to liver, bone or lymph nodes, providing a molecular basis for the long-observed clinical link between brain and lung metastasis. Among the functionally validated brain metastasis genes, the cyclooxygenase COX-2, the EGFR ligand HB-EGF, and the brain-specific Î±2-6 sialyltransferase ST6GALNAC5 mediate cancer cell passage through the blood-brain barrier. Other brain metastasis genes encode inflammatory factors and brain-specific proteolytic regulators, suggesting a multifaceted program for breast cancer colonization of the brain. Experiment Overall Design: Two different breast cancer cell lines, MDA-MB-231 and freshly isolated pleural effusion CN34 were used in this study. The MDA-MB-231 group contains three biological replicates of the parental, unselected population, and 4 brain metastatic isolates. CN34 contains 2 biological replicates of the parental, unselected population, and 4 brain metastatic isolates. In each case, the parental population was compared to the brain metastatic isolates to identify gene expression changes associated with the brain metastatic phenotype.

2009-05-16 | E-GEOD-12237 | biostudies-arrayexpress

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