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Glutamine sensitivity analysis identifies the xCT antiporter as a common triple negative breast tumor therapeutic target.

ABSTRACT: A small number of tumor-derived cell lines have formed the mainstay of cancer therapeutic development, yielding drugs with impact typically measured as months to disease progression. To develop more effective breast cancer therapeutics, and more readily understand their potential clinical impact, we constructed a functional metabolic portrait of 46 independently-derived breast tumorigenic cell lines, contrasted with purified normal breast epithelial subsets, freshly isolated pleural effusion breast tumor samples and culture-adapted, non-tumorigenic mammary epithelial cell derivatives. We report our analysis of glutamine uptake, dependence, and identification of a significant subset of triple negative samples that are glutamine auxotrophs. This NCBI GEO submission comprises a small datasest generated to compare the expression profiles of the above nontumorigenic, purified normal and purified pleural effusion samples with 10 established breast cancer-derived cell lines. This dataset was subsequently merged with a previously published expression dataset derived from 45 independent breast cancer derived cell lines (Neve, et al 2006), and analyses contrasting various subsets of the merged dataset were published. Expression data from 26 samples, no replicates: purified normal human mammary epithelial breast cellular subsets CD10+, BerEP4+, and remaining stromal cell samples from 3 independent anonymous donors; 3 anonymous purified human breast cancer pleural effusion samples; 4 HMEC-derived culture adapted but not transformed samples (184A1, 184B5, HMLE, HMLE-PR); and 10 established human breast cancer cell lines.

ORGANISM(S): Homo sapiens

SUBMITTER: Luika Timmerman

PROVIDER: E-GEOD-48984 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Glutamine sensitivity analysis identifies the xCT antiporter as a common triple negative breast tumor therapeutic target.

Project description:A small number of tumor-derived cell lines have formed the mainstay of cancer therapeutic development, yielding drugs with impact typically measured as months to disease progression. To develop more effective breast cancer therapeutics, and more readily understand their potential clinical impact, we constructed a functional metabolic portrait of 46 independently-derived breast tumorigenic cell lines, contrasted with purified normal breast epithelial subsets, freshly isolated pleural effusion breast tumor samples and culture-adapted, non-tumorigenic mammary epithelial cell derivatives. We report our analysis of glutamine uptake, dependence, and identification of a significant subset of triple negative samples that are glutamine auxotrophs. This NCBI GEO submission comprises a small datasest generated to compare the expression profiles of the above nontumorigenic, purified normal and purified pleural effusion samples with 10 established breast cancer-derived cell lines. This dataset was subsequently merged with a previously published expression dataset derived from 45 independent breast cancer derived cell lines (Neve, et al 2006), and analyses contrasting various subsets of the merged dataset were published.

2013-11-22 | GSE48984 | GEO

Expression data from DKAT and other breast cancer cell lines under baseline growth conditions

2012-06-01 | GSE33145 | GEO

The microRNA-205 is correlated to metastatic potential of 21T series: a breast cancer progression model

Project description:To gain insights into the mechanisms involved in breast cancer progression we conducted a microRNA global expression analysis on a 21T series of cell lines obtained from the same patient during different stages of breast cancer progression. These stages are represented by cell lines derived from normal epithelial (16N), atypical ductal hyperplasia (21PT), primary in situ ductal carcinoma (21NT) and pleural effusion of a lung metastasis (21MT-1 and 21MT-2). In a global microRNA expression analysis, miR-205 was the only miRNA to display an important downregulation in the metastatic cell lines (21MT-1; 21MT-2) when compared to the non-invasive cells (21PT and 21NT). The lower amounts of miR-205 found also correlated with high histological grades biopsies and with higher invasion rates in a Boyden chamber assay. This work pinpoints miR-205 as a potential player in breast tumor invasiveness. These experiments are conducted as 2 replicates.

2017-05-03 | E-MTAB-5239 | biostudies-arrayexpress

Expression data from DKAT and other breast cancer cell lines under baseline growth conditions

Project description:The DKAT cell line is a novel model of triple-negative breast cancer that was isolated from the pleural effusion of a 35 year-old caucasian woman with triple-negative breast cancer. We used microarrays to look at gene expression in the DKAT cell line compared to several other commonly-used breast cancer cell lines as well as a previously published data set in order to determine the molecular subtype of the DKAT cell line. DKAT, HMEC, and MDA-MB-231 cells were cultured in Mammary Epithelial Growth Media (MEGM, Lonza). RNA was isolated using Qiagen RNeasy kit and hybridization on Affymetrix microarrays was performed. Three separate cDNA reactions were performed and these were run as replicates.

2012-05-31 | E-GEOD-33145 | biostudies-arrayexpress

Microarray expression profiles of circular RNA in malignant pleural effusion

Project description:To explore the expression pattern of circular RNAs (circRNAs) and their biological functions in malignant pleural effusion, we surveyed the circRNA expression profiles of 3 lung adenocarcinoma-associated malignant pleural effusion (LA-MPE) and 3 tuberculous pleural effusion (TPE) from clinical patients using Clariom D human microarray.

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Mapping the soluble human leukocyte antigen peptidome of pleural effusions reveals lung and tumor-associated antigens

Project description:Soluble HLA (sHLA) molecules released to the plasma, carry their original peptide cargo and provide insight into the protein synthesis and degradation schemes of their source cells and tissues. Other body fluids, such as pleural effusions, may also contain sHLA-peptide complexes, and can potentially serve as a source of tumor antigens since these fluids are drained from the tumor microenvironment. Thus, we developed a methodology for purifying and analysing large pleural effusion sHLA class I peptidomes of patients inflicted with malignancies or benign diseases. The cleared pleural fluids, the cell pellets present in the pleural effusions, and the primary tumor cells cultured from cancer patients’ effusions, were used for immunoaffinity purification of the HLA molecules. The recovered HLA peptides were analyzed by capillary chromatography coupled to tandem mass spectrometry and the resulting LC-MS/MS data was analyzed with the MaxQuant software tool. Large HLA peptidomes were obtained by the analysis of the pleural effusions. The majority of peptides identified from the pleural effusions were defined as HLA ligands that fit the patients’ HLA consensus sequence motifs. The membranal and soluble HLA peptidomes of each individual patient were somewhat similar to each other. Many of the HLA peptides were derived from known tumor-associated antigens, lung-related proteins, and VEGF pathway proteins. Thus, the pleural effusion HLA peptidome of patients with malignant tumors can serve as a rich source of biomarkers for tumor diagnosis and personalized immunotherapy.

2022-05-25 | PXD027766 | Pride

FC-IBC-02: A New in vitro-in vivo Model of Triple Negative Inflammatory Breast Cancer

Project description:Inflammatory breast cancer (IBC) is the most aggressive type of advanced breast cancer and is associated with a poor prognosis. We have developed a new model of IBC derivated from the pleural effusion of a 49-year-old woman with metastatic secondary IBC. FC-IBC02 tumor cells were isolated from the pleural effusion and cultured under non-adherent conditions, resulting in the formation of spheroids or mammospheres. FC-IBC02 are triple negative (estrogen receptor negative, progesterone receptor negative and ErbB2 negative) and strongly positive for E-cadherin, beta-catenin and vimentin. FC-IBC02 cells developed breast tumors when they were injected into the mammary fat pad of SCID mice and characteristic tumor emboli were detected. Breast tumor xenografts were poorly differentiated triple negative carcinomas and all injected mice developed metastasis in the lungs and lymph nodes. These IBC tumor cells showed genomic alterations in all chromosomes, with the gains/amplifications more common than the deletions/losses. Duplicated regions were on 1q, 2p, 3q, 8q and 18p and chromosomes 7 and 9. The 8q chromosome arm where the MYC oncogene resides was amplified up to seven fold. Chromothripsis (local chromosome shattering) was observed on chromosome 11q and losses were found on 8p, 11q, 16q and 17p (location of TP53). FC-IBC-02 cells expressed the stem cell marker CD44, EpCAM and strongly expressed EGFR and ALK. In summary, this novel preclinical model demonstrated that IBC is a disease enriched for highly tumorigenic cells which harbor a stem cell phenotype. This IBC model is ideal for the study of the metastatic process and to evaluate targeting therapeutic modalities. Total RNA were isolated from IBC-02, IBC-02 in mammosphere growth, IBC3, SUM149, SUM190, MDA-MB231, and MDA-MB468 cell lines. Affymetrix Human U133 Plus 2.0 arrays were used for whole-genome gene expression assays. Duplicate samples were analyzed for each cell line.

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Quantitative proteomics revealed novel protein biomarkers to distinguish malignant pleural effusion from benign pleural effusion

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2024-03-08 | PXD050477 |

Copy number variations analysis by CytoscanHD array of 33 human pleural mesothelioma cell lines

Project description:We performed a cytoscanHD array to analyze copy number variations in the genome of 33 human pleural mesothelioma cell lines established from patient pleural effusion. We were particularly interested in the analysis of the p21.3 region of chromosome 9 which contains CDKN2A tumor suppressor genes and the gene encoding type I interferons that are often deleted and confer sensitivity to oncolytic Measles virus

2019-07-17 | GSE134349 | GEO

Intrapleural hypotonic cisplatin treatment for malignant pleural effusion in non-small cell lung cancer patients with intestinal lung disease. A multicenter non randomized trial.

Project description:Interventions: Multicenter, single-arm, open-label trial Primary outcome(s): The pleural effusion control rate (30days after administration of hypotonic cisplatin for malignant pleural effusion) Study Design: Single arm Non-randomized

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