Isolation and characterization of a metastatic hybrid cell line generated by ER negative and ER positive breast cancer cells in mouse bone marrow
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE27515 | GEO | 2011/05/25
SECONDARY ACCESSION(S): PRJNA138583
REPOSITORIES: GEO
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Project description:The origin and the contribution of breast tumor heterogeneity to its progression are not clear. We investigated the effect of a growing orthotopic tumor formed by an aggressive estrogen receptor (ER)-negative breast cancer cell line on the metastatic potential of a less aggressive ER-positive breast cancer cell line for the elucidation of how the presence of heterogeneous cancer cells might affect each other’s metastatic behavior. ER positive ZR-75-1/GFP/puro cells, resistant to puromycin and non-tumorigenic/non-metastatic without exogenous estrogen supplementation, were injected intracardiacally into mice bearing growing orthotopic tumors, formed by ER negative MDA-MB-231/GFP/Neo cells resistant to G418. A variant cell line B6, containing both estrogen-dependent and -independent cells, were isolated from GFP expressing cells in the bone marrow and re-inoculated in nude mice to generate an estrogen-independent cell line B6TC.
2011-05-25 | E-GEOD-27515 | biostudies-arrayexpress
Project description:Up to 40% of patients with Estrogen Receptor positive (ER+) breast cancer experience relapse. Breast cancer stem cells (BCSCs) are known to be involved in therapy resistance, relapse, and development of more aggressive and metastatic tumors. Therefore, there is an urgent need to identify genes/pathways that drive stem-like cell properties in ER+ breast tumors. Using single-cell RNA sequencing and bioinformatic approaches, with additional follow-up studies, we identified a unique quiescent stem-like cell population that is driven by ER and NFkB in multiple ER+ breast cancer models. Moreover, a gene signature derived from this stem-like population is expressed in endocrine therapy-resistant and metastatic cell populations and predictive of poor patient outcome. These findings indicate a novel role for ER and NFkB crosstalk in BCSCs biology and understanding the mechanism by which these pathways promote stem properties may be exploited to improve outcomes for ER+ breast cancer patients at risk of relapse.
2022-12-16 | GSE205415 | GEO
Project description:Interleukin 6 (IL6) signaling has been associated with an aggressive and metastatic phenotype in multiple solid tumors including breast cancer, but its mechanism of action in mediating tumor progression and treatment response is not clear. By exploiting a clinically relevant intraductal xenograft model of estrogen receptor positive (ER+) breast cancer, we demonstrate that IL6 increases both primary tumor growth and distant metastases. By integrating pre-clinical models and clinical specimens, we show that signal transducer and activator of transcription 3 (STAT3) mediates IL6-induced activation of a metastatic gene program from enhancer-elements shared with ER and its pioneer factor FOXA1. Although IL6 activated STAT3 and ER/FOXA1 share cis-regulatory regions, STAT3 drives transcription independent of ER and FOXA1 function, and the IL6/STAT3 gene program is not influenced by ER-targeted therapies, decoupling these two important pathways. This demonstrates that ER/FOXA1 and IL6/STAT3 are two parallel, but independent actionable pathways controlling breast cancer progression.
2021-09-08 | PXD012980 | Pride
Project description:Interleukin 6 (IL6) signaling has been associated with an aggressive and metastatic phenotype in multiple solid tumors including breast cancer, but its mechanism of action in mediating tumor progression and treatment response is not clear. By exploiting a clinically relevant intraductal xenograft model of estrogen receptor a positive (ER+) breast cancer, we demonstrate that IL6 increases both primary tumor growth and distant metastases. In pre-clinical models and clinical specimens, signal transducer and activator of transcription 3 (STAT3) mediates IL6-induced activation of a metastatic gene program from enhancers shared with ER and its pioneer factor FOXA1. However, STAT3 drives transcription independent of ER and FOXA1 function from these enhancers, and the IL6/STAT3 pathway is therefore resistant to ER-targeted therapies, decoupling these two important oncogenic pathways. This demonstrates that ER/FOXA1 and IL6/STAT3 are two parallel, but functionally independent and actionable pathways controlling breast cancer progression.
2020-07-17 | GSE126003 | GEO
Project description:Interleukin 6 (IL6) signaling has been associated with an aggressive and metastatic phenotype in multiple solid tumors including breast cancer, but its mechanism of action in mediating tumor progression and treatment response is not clear. By exploiting a clinically relevant intraductal xenograft model of estrogen receptor positive (ER+) breast cancer, we demonstrate that IL6 increases both primary tumor growth and distant metastases. By integrating pre-clinical models and clinical specimens, we show that signal transducer and activator of transcription 3 (STAT3) mediates IL6-induced activation of a metastatic gene program from enhancer-elements shared with ER and its pioneer factor FOXA1. Although IL6 activated STAT3 and ER/FOXA1 share cis-regulatory regions, STAT3 drives transcription independent of ER and FOXA1 function, and the IL6/STAT3 gene program is not influenced by ER-targeted therapies, decoupling these two important pathways. This demonstrates that ER/FOXA1 and IL6/STAT3 are two parallel, but independent actionable pathways controlling breast cancer progression.
2020-07-17 | GSE126004 | GEO
Project description:Interleukin 6 (IL6) signaling has been associated with an aggressive and metastatic phenotype in multiple solid tumors including breast cancer, but its mechanism of action in mediating tumor progression and treatment response is not clear. By exploiting a clinically relevant intraductal xenograft model of estrogen receptor positive (ER+) breast cancer, we demonstrate that IL6 increases both primary tumor growth and distant metastases. By integrating pre-clinical models and clinical specimens, we show that signal transducer and activator of transcription 3 (STAT3) mediates IL6-induced activation of a metastatic gene program from enhancer-elements shared with ER and its pioneer factor FOXA1. Although IL6 activated STAT3 and ER/FOXA1 share cis-regulatory regions, STAT3 drives transcription independent of ER and FOXA1 function, and the IL6/STAT3 gene program is not influenced by ER-targeted therapies, decoupling these two important pathways. This demonstrates that ER/FOXA1 and IL6/STAT3 are two parallel, but independent actionable pathways controlling breast cancer progression.
2020-07-17 | GSE150131 | GEO
Project description:Response and Resistance to ER-directed Therapy in ER+ Metastatic Breast Cancer
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Project description:Background MicroRNA expression is frequently dysregulated in cancer and it could be used potentially as a disease classifier and a prognostic tool in cancer. It has been reported that the cancer associated specific microRNAs were stably detected in blood. The objective of this study was to discover a panel of circulating microRNAs as potential ER+/HER2- breast cancer biomarkers. Methods We compared levels of circulating microRNAs in blood samples from 11 ER+/HER2- advanced breast cancer patients with age-matched 5 control subjects by using microarray-based expression profiling. We validated the level of microRNAs by real-time quantitative polymerase cycle reaction (RT-qPCR) in 40 control subjects, 180 early breast cancer patients (EBC), and 52 metastatic breast cancer patients (MBC). Then, we assessed the association between the levels of microRNA and clinical outcomes of ER+/HER2- metastatic breast cancer. Background MicroRNA expression is frequently dysregulated in cancer and it could be used potentially as a disease classifier and a prognostic tool in cancer. It has been reported that the cancer associated specific microRNAs were stably detected in blood. The objective of this study was to discover a panel of circulating microRNAs as potential ER+/HER2- breast cancer biomarkers. Methods We compared levels of circulating microRNAs in blood samples from 11 ER+/HER2- advanced breast cancer patients with age-matched 5 control subjects by using microarray-based expression profiling. We validated the level of microRNAs by real-time quantitative polymerase cycle reaction (RT-qPCR) in 40 control subjects, 180 early breast cancer patients (EBC), and 52 metastatic breast cancer patients (MBC). Then, we assessed the association between the levels of microRNA and clinical outcomes of ER+/HER2- metastatic breast cancer. Controls: 5 cases; ER +/HER2- breast cancer patients : 11 cases
2013-12-12 | E-GEOD-53179 | biostudies-arrayexpress
Project description:Patients diagnosed with estrogen receptor (ER) positive breast cancer have a prolonged risk of distal metastatic recurrence to vital organs. Metastatic disease is incurable at present due to the development of treatment resistant cell populations. Here we used single-cell RNA sequencing to evaluate the transcriptome heterogeneity of ER+ breast cancer patient-derived xenografts (PDX) tropic for three common breast cancer metastatic sites – bone, brain, and liver – compared to primary tumors grown in the mammary fat pad. Metastatic cell populations at each location were phenotypically distinct from primary tumor cells with unique transcriptional programs indicative of signaling programs driven by specific transcription factors. Cells that metastasized to brain and liver tissue adopted gene expression programs indicative of the target organ microenvironments. Discerning the organ-specific phenotypic adaptations of metastatic ER+ breast cancer cells may help tailor appropriate therapies for individual patients and to each metastatic site.
2020-05-09 | GSE131007 | GEO
Project description:Estrogen receptor positive (ER+) breast cancers that develop resistance to therapies that target the ER are the most common cause of breast cancer death. Beyond mutations in ER, which occur in 25-30% of patients treated with aromatase inhibitors (AIs), our understanding of clinical mechanisms of resistance to ER-directed therapies remains incomplete. We identified activating HER2 mutations in metastatic biopsies from eight patients with ER+ metastatic breast cancer who had developed resistance to ER-directed agents, including AIs, tamoxifen, and fulvestrant. Examination of treatment-naïve primary tumors in five patients revealed no evidence of pre-existing mutations in four of five patients, suggesting that these mutations were acquired under the selective pressure of ER-directed therapy. These mutations were mutually exclusive with ER mutations, suggesting a distinct mechanism of acquired resistance to ER-directed therapies. In vitro analysis confirmed that these mutations conferred estrogen independence. In addition, and in contrast to ER mutations, these mutations resulted in resistance to tamoxifen, fulvestrant, and the CDK4/6 inhibitor palbociclib. Resistance was overcome by combining ER-directed therapy with the irreversible HER2 kinase inhibitor neratinib, highlighting an effective treatment strategy in these patients.
2018-10-19 | GSE121411 | GEO