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Expression profiles of CD24-/CD44+/ESA+ population in MDA-MB-231 and its highly metastatic variants.

ABSTRACT: Breast cancer is a curable disease if it is diagnosed at an early stage. However, only little options are left once the tumor is metastasized to distant organs, and more than 90% of breast cancer death is attributed to metastatic disease. The process of metastasis is highly complex and involves many steps for successful colonization of tumor cells at a target organ. According to the cancer stem cell (CSC) theory, which still remains a hypothesis, these metastatic cells must have stem cell-like capability for their self-renewal in addition to their invasive ability. Therefore, it has been predicted that a “metastatic stem cell”, which is distinct from a cancer stem cell, must exist in the primary tumor mass. To identify genes that are involved in metastasis of CSCs, we isolated CSC populations from a well-established model cell line of breast cancer, MDA-MB231, and that of highly metastatic variants, 231BoM-1833 and 231BrM-2a, using CD24, CD44 and EpCAM (ESA), which have been identified as surface markers for CSCs in breast cancers. Overall yield of CSCs from these cells ranged from 2% to 4%. We then performed global expression profile analysis for these CSCs using the Affymetrix Human Gene 1.0ST array.

ORGANISM(S): Homo sapiens

PROVIDER: GSE25976 | GEO | 2011/11/30

SECONDARY ACCESSION(S): PRJNA135451

REPOSITORIES: GEO

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Expression profiles of CD24-/CD44+/ESA+ population in MDA-MB-231 and its highly metastatic variants.

Project description:Breast cancer is a curable disease if it is diagnosed at an early stage. However, only little options are left once the tumor is metastasized to distant organs, and more than 90% of breast cancer death is attributed to metastatic disease. The process of metastasis is highly complex and involves many steps for successful colonization of tumor cells at a target organ. According to the cancer stem cell (CSC) theory, which still remains a hypothesis, these metastatic cells must have stem cell-like capability for their self-renewal in addition to their invasive ability. Therefore, it has been predicted that a “metastatic stem cell”, which is distinct from a cancer stem cell, must exist in the primary tumor mass. To identify genes that are involved in metastasis of CSCs, we isolated CSC populations from a well-established model cell line of breast cancer, MDA-MB231, and that of highly metastatic variants, 231BoM-1833 and 231BrM-2a, using CD24, CD44 and EpCAM (ESA), which have been identified as surface markers for CSCs in breast cancers. Overall yield of CSCs from these cells ranged from 2% to 4%. We then performed global expression profile analysis for these CSCs using the Affymetrix Human Gene 1.0ST array. CSC populations (CD24-/CD44+/ESA+) from MDA-MB231, 231BoM-1833 and 231BrM-2a were isolated by magnetic-activated cell sorting (MACS) using specific antibodies to these surface markers. The total RNA was isolated from the CSC populations using the RNeasy RNA isolation kit (Qiagen). The RNA was then converted to cDNA and they were hybridized to the Human Gene 1.0ST chip (Affymetrix). The data was normalized using the RMA algorithm of the Expression Console software (Affymetrix). A comparison of transcriptional profiles was then performed in CSCs of highly metastatic cell lines (231BoM-1833 and 231BrM-2a) compared to the CSCs of MDA-MB-231.

2011-11-30 | E-GEOD-25976 | biostudies-arrayexpress

Cancer stem cells from lobular infiltrating breast tumor metastasize to bone and acquire a gene signature associated to bone tropism

Project description:We investigated the role of breast cancer stem-like cells (CSCs-like), isolated from primary tumor, in promoting bone metastases in a human-in-mice model. Luciferase-transduced CD44+CD24- breast CSCs-like were injected through subcutaneous (SC) and intracardiac (IC) route in nonobese/severe combined immunodeficient (NOD/SCID) mice carrying subcutaneous human bone implants. The implanted bone was viable, active and human neo-vascularization was present. By in vivo luciferase imaging, we monitored tumor growth and detected bone-localized breast CSCs-like, both after SC and IC injection. Bone metastatic lesions were histologically evident, and tumor cells expressed epithelial markers and vimentin. Bone metastatic cells isolated from bone implants showed a CD44-CD24+ phenotype and re-created tumors and bone metastases after injection in secondary mice. A “bone tropism” expression signature was found to distinguish bone-colonizing cells from parental CSCs-like and to persist at subsequent passages also in the absence of surrounding bone tissue. The bone tropism signature displayed significant enrichment in genes discriminating bone metastases of breast cancer from metastases at other organs. Our results demonstrate the ability of breast CSCs-like to promote bone metastasis and provide a CSCs-like bone tropism signature, with potential prognostic value. C10 breast cancer stem-like cells (CSCs-like) were derived as mammospheres from a lobular-infiltrating breast carcinoma (ER+, HER2-). Samples are organized in the following groups: (i) Breast CSCs-like (C10, duplicate); (ii) Luciferase-transduced CSCs-like (C10L, simplicate); (iii) Bone-isolated C10L metastatic cells (C10-bone, duplicate) and subsequently (iv) grown in vitro as spheroids (C10-CSC, simplicate) or (v) re-grown in subcutaneous implants (C10-SC, duplicate).

2013-11-30 | E-GEOD-36102 | biostudies-arrayexpress

Transcription profiling of human HMLER breast cancer cells treated with paclitaxel and salinomycin-treated HMLER breast cancer cells

Project description:Screens for agents that specifically kill epithelial cancer stem cells (CSCs) have not been possible due to the rarity of these cells within tumor cell populations and their relative instability in culture. We describe here an approach to screening for agents with epithelial CSC-specific toxicity. We implemented this method in a chemical screen and discovered compounds showing selective toxicity for breast CSCs. One compound, salinomycin, reduces the proportion of CSCs by >100-fold relative to paclitaxel, a commonly used breast cancer chemotherapeutic drug. Treatment of mice with salinomycin inhibits mammary tumor growth in vivo and induces increased epithelial differentiation of tumor cells. In addition, global gene expression analyses show that salinomycin treatment results in the loss of expression of breast CSC genes previously identified by analyses of breast tissues isolated directly from patients. This study demonstrates the ability to identify agents with specific toxicity for epithelial CSCs Experiment Overall Design: Experimentally transformed HMLER breast cancer cells were treated in culture with either paclitaxel (10nM) or salinomycin (1uM) for one week. There were three biologic replicates for each treatment condition.

2009-09-15 | E-GEOD-17215 | biostudies-arrayexpress

Increased cholesterol biosynthesis identified as a key feature and a therapeutic target of cancer stem cells as revealed by proteomic comparison of clinical breast cancer tissue and corresponding patient-derived xenografts and mammospheres

Project description:Cancer stem cells (CSCs) comprise a small subpopulation of undifferentiated cancer cells with the ability to self-renew and give rise to the heterogeneous cancer cell lineages that form tumorous masses. Thus, tumor eradication may be greatly improved by specifically targeting CSCs, as they exhibit resistance to conventional therapy. To gain insight into the unique biology of CSCs, we developed patient-derived xenograft (PDX) tumors from ER-negative breast cancer patient tissue from which we isolated mammospheres, a method known to enrich for cells with CSC-properties. An unbiased, comparative global proteomic analysis using label-free mass spectrometry was performed on the patient tumor tissues and corresponding PDX tumors and mammospheres. Good concordance between the proteome profiles of patient tumor tissue and corresponding PDX tumors was observed. However, lower abundance of immune- and extracellular matrix-related proteins and higher abundance of proteins associated with cell-to-cell adhesion including desmosome proteins and β-catenin were observed in PDX versus patient tumors. Interestingly, analysis of proteins elevated in mammospheres vs. PDX tumors identified an enrichment of proteins associated with de novo cholesterol synthesis. The clinical relevance of increased cholesterol biosynthesis protein expression was verified in a large gene expression data set of clinical breast cancers showing correlation with shorter relapse-free survival. RNA interference and chemical inhibition of the cholesterol biosynthesis pathway reduced mammosphere formation and growth of CSCs derived from PDX tumors and cancer cell lines. Our findings identify the cholesterol biosynthesis pathway as central for CSC growth and a potential therapeutic target for CSC as well as providing an additional mechanistic explanation for the observed benefit of statins in breast cancer treatment.

2019-07-02 | PXD011222 | Pride

Lateral interactions between B7-H3 and CD147 are essential for stemness in breast cancer: a novel insight from proximal proteome analysis

Project description:Oncogenic cell-surface membrane proteins contribute to the phenotypic and functional characteristics of cancer stem cells (CSCs). We quantitatively analyzed cell-surface membrane proteins that are in close proximity to CD147 in CSCs using proximity-labeling proteomic approach. Moreover, we compared CSCs to non-CSCs to identify CSC-specific cell-surface membrane proteins that are the nearest neighbors of CD147 and revealed that lateral interaction between CD147 and CD276 (B7H3) concealed within the lipid raft microdomain in CSCs confers resistance to docetaxel, known to treat many types of cancer patients including metastatic breast cancer. Furthermore, we found that co-expression of CD147 and CD276 in patients with HER2+ breast cancer who received chemotherapy had poor disease-free survival (DFS) and Overall survival (OS) rates (p = 0.04 and 0.08, respectively). Subsequent immunohistochemical analysis indicated that co-expression of CD147 and CD276 may be associated with poor response to chemotherapy in an independent HER2+ BC cohort. Altogether, our study suggests that the lateral interaction between CD147 and its proximal partners, such as CD276, may be related to a poor prognostic factor in BC and a predictive marker for the critical phenotypic determinant of breast cancer stemness.

2023-10-24 | PXD036909 | Pride

Comparison of gene expression in CSCs (tumorspheres) vs non-CSCs (2D adherent condition) from A13A PDAC cell line [RNA-seq]

Project description:Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest and most metastatic cancers in human. PDACs respond poorly to therapies, partly due to cancer stem cells (CSCs) that self-renew, survive chemotherapies, metastasise and replenish the tumor. Factors secreted by tumor cells mediate autocrine/paracrine crosstalk with surrounding cells contributing to the stem cell niche but are still insufficiently characterised. Here we used quantitative SILAC proteomics to identify secreted factors enriched in CSC secretome compared to non-CSCs. Our data uncovered factors that mediate the crosstalk between CSCs and non-CSCs as well as genes mediating the gene expression circuitries regulating CSC proliferation.

2024-02-18 | GSE244287 | GEO

Comparison of gene expression in CSCs (tumorspheres) vs non-CSCs (2D adherent condition) from A13A PDAC cell line [ATAC-seq]

2024-02-18 | GSE244326 | GEO

Expression of miR-200c in claudin-low breast cancer alters stem cell functionality, enhances chemosensitivity and reduces metastatic potential

Project description:Claudin-low tumors are a highly aggressive breast cancer subtype with no targeted treatments and a clinically documented resistance to chemotherapy. They are significantly enriched in cancer stem cells (CSCs), which makes claudin-low tumor models particularly attractive for studying CSC behavior and developing novel approaches to minimize CSC therapy resistance. One proposed mechanism by which CSCs arise is via an epithelial-mesenchymal transition (EMT), and reversal of this process may provide a potential therapeutic approach for increasing tumor chemosensitivity. Therefore, we investigated the role of the miR-200 family of microRNAs in regulating the epithelial state, stem-like properties, and therapeutic response in an in vivo primary, syngeneic p53null claudin-low tumor model that is normally deficient in miR-200 expression. Using an inducible lentiviral approach, we expressed the miR-200c cluster in this claudin-low model and found that it changed the epithelial state, and consequently, impeded CSC behavior in these mesenchymal tumors. Moreover, these state changes were accompanied by a decrease in proliferation and an increase in the differentiation status. MiR-200c expression also forced a significant reorganization of tumor architecture, affecting important cellular processes involved in cell-cell contact, cell adhesion, and motility. Accordingly, induced miR200c expression also significantly enhanced the chemosensitivity and decreased the metastatic potential of this p53null claudin-low tumor model. Collectively, our data suggest that miR-200c expression in claudin-low tumors offers a potential therapeutic application to disrupt the EMT program on multiple fronts in this mesenchymal tumor subtype, by altering tumor growth, chemosensitivity, and metastatic potential in vivo. reference x sample

2015-06-22 | E-GEOD-62230 | biostudies-arrayexpress

c-Src functionality controls self-renewal, tumorigenicity and glucose metabolism in breast cancer stem cells

Project description:Deregulation of Src kinases is associated with cancer. We previously showed that SrcDN conditional expression in MCF7 cells diminished tumorigenesis and causes tumor regression in mice. However, it remained unclear whether SrcDN affected breast cancer stem cell functionality or it reduced tumor mass. Here, we address this question by isolating an enriched population of BCSCs (ESA+-CD44+-CD24-) and the tumor-differentiated cells (ESA+-CD44+-CD24+) from MCF7-Tet-On-SrcDN. ESA+-CD44+-CD24- grew in suspension forming mammospheres, and producing tumors in nude mice, while ESA+-CD44+-CD24+ were poorly/non-tumorigenic. Doxycycline-induction of SrcDN inhibited BCSC tumorigenesis, selfrenewal, and stem-cell markers expression. SrcDN significantly inhibited SFE, and stem-cell markers expression in triple-negative breast cancer (TNBC) MDA-MB-231 and SUM159PT cells. Inducible depletion of c-Src caused similar effects in MDA-MB-231 cells. In MCF7-Tet-On-SrcDN derived mammospheres SrcDN-induction inhibited expression, and activity of hexokinase, pyruvate kinase and lactate dehydrogenase, resulting in diminished glucose consumption and lactate production, which restricted Warburg effect. Thus, c-Src functionality is important for breast cancer stem cell maintenance and renewal, tumorigenicity, and stem cell transcription factor expression, effects linked to glucose metabolism reduction.

2020-07-23 | PXD017789 | Pride

RNA-seq gene expression of flow cytometry sorted breast cancer stem cell populations

Project description:MMTV-PyMT transgenic FVBN mice spontaneously developed breast tumors. Two tumors were collected as replicate samples, and cells from the dissociated tissue were sorted into 2 cancer stem cell (CSC) populations, along with the remaining non-CSCs. The samples were submitted for RNAseq to generate differential gene expression profiles of the breast tumor CSC populations.

2021-11-21 | GSE189223 | GEO

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