Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA174095 | ENA |
REPOSITORIES: ENA
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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.
2012-09-20 | E-GEOD-40464 | biostudies-arrayexpress
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.
2012-09-20 | GSE40464 | GEO
Project description:CEP-37440 at low concentration (1,000 nM) decreased the proliferation of the human inflammatory breast cancer (IBC) cell line FC-IBC02, while not affecting the proliferation of normal breast epithelial cells. CEP-37440 decreased the cell proliferation of FC-IBC02 by blocking the auto-phosphorylation kinase activity of FAK (Tyr 397). This cell line did not expressed ALK. In vivo, CEP-37440 significantly decreased FC-IBC02 breast tumor xenografts growth with maximum of 40% tumor growth inhibition. None of the FC-IBC02 breast xenografts mice treated with CEP-37440 developed brain metastasis in contrast to the control group in which 20% of the mice developed brain metastasis. Expression array analyses in FC-IBC02 cells showed that CEP-37440 affects the expression of genes related to apoptosis specifically related to the interferon signaling pathway. Cell proliferation assays were performed in the presence of several concentrations of CEP-37440 using IBC and triple negative breast cancer (TNBC) non-IBC cell lines. We studied the expression of total FAK1, phospho-FAK1 (Tyr 397), total ALK and phospho-ALK (Tyr 1604) in these cells by ELISA. FC-IBC02 cells were treated with 1,000 nM CEP-37440 during 48 h, and expression arrays were performed in order to define pathways dysregulated by CEP-37440.
2015-12-14 | E-GEOD-73285 | biostudies-arrayexpress
Project description:Purpose: Transcriptome profiling (RNA-seq) of a novel human Inflammatory Breast Cancer cell line A3250 in comparison to SUM149 and MDA-MB-231 Inflammatory Breast Cancer (IBC) is the most aggressive form of breast cancer with distinct clinical and histopathological features, but understanding of the unique aspects of IBC biology lags far behind that of other breast cancers. We describe a novel triple-negative IBC cell line, A3250, that recapitulates key features of human IBC in a mouse xenograft model.The purpose of this study was to compare differences in gene expression between A3250 IBC, MDA-MB-231 non-IBC and SUM149 IBC that does not present with typical clinical sympotms of IBC in a mouse model, with the goal of identifying unique molecular features for this unique type of breast cancer Results: RNA-Seq analysis identified expression profile characteristic for the novel A3250 IBC cell line, compared to SUM149 IBC and MDA-MB-231 non-IBC.
2021-10-01 | GSE180788 | GEO
Project description:Inflammatory Breast Cancer (IBC) is the most aggressive form of breast cancer, but understanding of the unique aspects of IBC biology lags far behind that of other breast cancers. One of the key barriers in advancing understanding of the molecular determinants of IBC has been the lack of adequate models for this disease that presents with distinct clinical and histopathological features. We describe here a novel human triple-negative IBC cell line, A3250, that recapitulates key features of human IBC in a mouse orthotopic model including skin erythema, diffuse tumor growth, high stroma to tumor ratio, dermal lymphatic invasion, and extensive lymph node and distant metastases. Tumor-associated macrophages were particularly enriched, and A3250 cells expressed very high levels of CCL2, a macrophage recruiting chemokine in the absence of detectable levels of its cognate receptor. CCL2 knockdown led to a striking reduction in macrophage densities, tumor cell proliferation, and metastasis in vivo. These results identify tumor-derived CCL2 as a key factor driving macrophage expansion and indirectly, the growth of A3250 IBC cells in vivo. Comparison of the A3250 chemokine expression profile with human IBC expression data sets revealed sharing of this profile across different IBC subtypes as well as enrichment for macrophage expression. Thus, this human IBC model provides a unique opportunity to uncover novel aspects of IBC biology, and to test novel therapies for this deadly disease.
2023-09-30 | GSE159987 | GEO
Project description:CEP-37440 at low concentration (1,000 nM) decreased the proliferation of the human inflammatory breast cancer (IBC) cell line FC-IBC02, while not affecting the proliferation of normal breast epithelial cells. CEP-37440 decreased the cell proliferation of FC-IBC02 by blocking the auto-phosphorylation kinase activity of FAK (Tyr 397). This cell line did not expressed ALK. In vivo, CEP-37440 significantly decreased FC-IBC02 breast tumor xenografts growth with maximum of 40% tumor growth inhibition. None of the FC-IBC02 breast xenografts mice treated with CEP-37440 developed brain metastasis in contrast to the control group in which 20% of the mice developed brain metastasis. Expression array analyses in FC-IBC02 cells showed that CEP-37440 affects the expression of genes related to apoptosis specifically related to the interferon signaling pathway.
2015-12-14 | GSE73285 | GEO
Project description:Inflammatory breast cancer (IBC) is a rare and aggressive type of breast cancer (BC) whose molecular basis is poorly understood. We performed a comprehensive molecular analysis of 24 fresh frozen IBC biopsies naïve of treatment, using a high-resolution microarray platform The most common genes covered by copy number alterations included gains of MYC and MDM4, and losses affecting TP53 and RB1. MYC and MDM4 genes have been related to IBC aggressiveness, and MDM4 might also represent a new therapeutic target in IBC. Thirteen IBC cases presented copy-neutral of heterozygosity (cnLOH) or losses covering CHL1, which gives additional evidence of its role as a tumor suppressor. Functional enrichment analysis with the most common alterations revealed genes associated with inflammatory regulation and immune response. Particularly, IL6R and IL7 could represent therapeutic targets for IBC treatment. Chromothripsis patterns were identified in nine cases and chromosomal instability in 50% of cases. High homologous recombination (HR) deficiency scores were observed in triple-negative IBC and those with metastasis. High telomeric allelic imbalance (TAI) score was detected in patients having worse overall survival (OS). TAI score could also be useful to predict deficiency in homologous recombination (HR) genes and to identify patients for platinum or PARP inhibitor therapy. Our study describes the most common genomic alterations in IBC and their association with clinical findings, providing a framework for improved diagnosis and therapeutic opportunities for this aggressive tumor type.
2020-01-24 | GSE144015 | GEO
Project description:Inflammatory breast cancer (IBC) is a unique clinical entity characterized by rapid onset of erythema and swelling of the breast often without an obvious breast mass. Many studies have examined and compared gene expression between IBC and non-IBC (nIBC), repeatedly finding clusters associated with receptor subtype, but no consistent gene signature associated with IBC has been validated. Here we examined microdissected IBC tumor cells compared to microdissected nIBC tumor cells matched based on estrogen and HER-2/neu receptor status. Genomic profiling of 20 inflammatory breast cancer (IBC), 20 non-IBC and 5 normal was studied.
2013-03-29 | E-GEOD-45582 | biostudies-arrayexpress
Project description:Inflammatory breast cancer (IBC) is a unique clinical entity characterized by rapid onset of erythema and swelling of the breast often without an obvious breast mass. Many studies have examined and compared gene expression between IBC and non-IBC (nIBC), repeatedly finding clusters associated with receptor subtype, but no consistent gene signature associated with IBC has been validated. Here we examined microdissected IBC tumor cells compared to microdissected nIBC tumor cells matched based on estrogen and HER-2/neu receptor status. Gene expression profiling of 20 inflammatory breast cancer (IBC), 20 non-IBC and 5 normal was studied.
2013-03-29 | E-GEOD-45581 | biostudies-arrayexpress
Project description:assess the efficacy of OTX015 (MK-8628) BET inhibitor in vitro and in vivo triple negative breast cancer models
2017-01-03 | GSE79721 | GEO