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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE40464 | GEO | 2012/09/20

SECONDARY ACCESSION(S): PRJNA174095

REPOSITORIES: GEO

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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.

2012-09-20 | E-GEOD-40464 | biostudies-arrayexpress

The effects of CEP-37440, an inhibitor of focal adhesion kinase, in vitro and in vivo on inflammatory breast cancer cells.

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

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. 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.

2013-11-22 | E-GEOD-48984 | biostudies-arrayexpress

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

2013-11-22 | GSE48984 | GEO

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

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.

2012-06-01 | GSE33145 | GEO

Intrapleural nano-immunotherapy promotes innate and adaptive immune responses to enhance anti-PD-L1 therapy for malignant pleural effusion

Project description:Malignant pleural effusion (MPE) is indicative of terminal malignancy with uniformly fatal prognosis. Often, two distinct compartments of tumor microenvironment, the effusion and disseminated pleural tumors, co-exist in the pleural cavity, presenting a major challenge for therapeutic interventions and drug delivery. Clinical evidence suggests that MPE comprises abundant tumor associated myeloid cells with the tumor-promoting phenotype, impairing antitumor immunity. Here, we developed liposomal cyclic dinucleotide (LNP-CDN) for targeted activation of STING signaling in macrophages and dendritic cells and showed that, upon intrapleural administration, they induce drastic changes in the transcriptional landscape in MPE, mitigating the immune cold MPE in both the effusion and pleural tumors. Moreover, combination immunotherapy with blockade of PD-L1 potently reduced MPE volume and inhibited tumor growth not only in pleural cavity but also in lung parenchyma, conferring significantly prolonged survival of MPE-bearing mice. Furthermore, the LNP-CDN-induced immunological effects were also observed with clinical MPE samples, suggesting the potential of intrapleural LNP-CDN for clinical MPE immunotherapy.

2021-09-21 | GSE164487 | GEO

Intrapleural nano-immunotherapy promotes innate and adaptive immune responses to enhance anti-PD-L1 therapy for malignant pleural effusion

2021-09-21 | GSE179783 | GEO

The effects of CEP-37440, an inhibitor of focal adhesion kinase, in vitro and in vivo on inflammatory breast cancer cells.

2015-12-14 | GSE73285 | GEO

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.

2023-05-01 | GSE122427 | GEO

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