Transcription profiling of human MCF10A cells co-cultured with breast fibroblasts from breast cancer tissues or normal breast tissues
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Sandya Liyanarachchi
PROVIDER: E-GEOD-10046 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:MCF10A series is one of the few human models of breast tumor progression. A derivative of MCF10A cells is the MCFDCIS, which reproducibly forms comedo DCIS-like lesions that spontaneously progress to invasive tumors. We used this model to explore the relative importance of myoepithelial cells and stromal fibroblasts in the in situ to invasive breast carcinoma transition. We use Affymetrix 11K XbaI or 250K StyI SNP arrays to analyze the MCF10A series cells and MCFDCIS derived xenografts for copy number changes and LOH (loss of heterozygosity). Keywords: Cell line, xenografts of time course/co-injection groups, different cell types isolated from xenografts
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Project description:The non-tumourigenic human breast epithelial cell line MCF10A is the cell line most commonly used as a model for normal human breast cells. This dataset provides a reference genome for MCF10A. The whole genome, high-throughput sequencing was performed using the Illumina NovaSeq 6000 PE150 system. Both NGS and bioinformatic analysis were performed by Novogene (UK).
2023-10-01 | E-MTAB-13191 | biostudies-arrayexpress
Project description:Background: E-cadherin is an adherens junction protein that forms homophilic intercellular contacts in epithelial cells while also interacting with the intracellular cytoskeletal networks. It has roles including establishment and maintenance of cell polarity, differentiation, migration and signalling in cell proliferation pathways. Its downregulation is commonly observed in epithelial tumours and is a hallmark of the epithelial to mesenchymal transition (EMT). Methods: To improve our understanding of how E-cadherin loss contributes to tumorigenicity, we investigated the impact of its elimination from the non-tumorigenic breast cell line MCF10A. We performed cell-based assays and whole genome RNAseq to characterize an isogenic MCF10A cell line that is devoid of CDH1 expression due to an engineered homozygous 4bp deletion in CDH1 exon 11. Results: The E-cadherin-deficient line, MCF10A CDH1-/- showed subtle morphological changes, weaker cell-substrate adhesion, delayed migration, but retained cell-cell contact, contact growth inhibition and anchorage-dependent growth. Within the cytoskeleton, the apical microtubule network in the CDH1-deficient cells lacked the radial pattern of organization present in the MCF10A cells and F-actin formed thicker, more numerous stress fibres in the basal part of the cell. Whole genome RNAseq identified compensatory changes in the genes involved in cell-cell adhesion while genes involved in cell-substrate adhesion, notably ITGA1, COL8A1, COL4A2 and COL12A1, were significantly downregulated. Key EMT markers including CDH2, FN1, VIM and VTN were not upregulated although increased expression of proteolytic matrix metalloprotease and kallikrein genes was observed. Conclusions: Overall, our results demonstrated that E-cadherin loss alone was insufficient to induce an EMT or enhance transforming potential in the non-tumorigenic MCF10A cells but was associated with broad transcriptional changes associated with tissue remodelling. Examination of the impact of E-cadherin (CDH1) loss in an isogenic pair of breast cell lines.
2014-08-01 | E-GEOD-59317 | biostudies-arrayexpress
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Project description:Basal-like breast cancer (BBC) is an aggressive subtype of breast cancer that has no biologically targeted therapy. The interactions of BBCs with stromal cells are important determinants of tumor biology, with inflammatory cells playing well-recognized roles in cancer progression. Despite the fact that macrophage–BBC communication is bidirectional, important questions remain about how BBCs affect adjacent immune cells. This study investigated monocyte-to-macrophage differentiation and polarization and gene expression in response to coculture with basal like versus luminal breast cancer cells. Changes induced by coculture were compared with changes observed under classical differentiation and polarization conditions. Monocytes (THP-1 cells) exposed to BBC cells in coculture had altered gene expression with upregulation of both M1 and M2 macrophage markers. Two sets of M1 and M2 markers were selected from the PCR profiles and used for dual immunofluorescent staining of BBC versus luminal cocultured THP-1s, and cancer-adjacent, benign tissue sections from patients diagnosed with BBCs or luminal breast cancer, confirming the differential expression patterns. Relative to luminal breast cancers, BBCs also increased differentiation of monocytes to macrophages and stimulated macrophage migration. Consistent with these changes in cellular phenotype, a distinct pattern of cytokine secretion was evident in macrophage–BBC cocultures, including upregulation of NAP-2, osteoprotegerin, MIG, MCP-1, MCP-3, and interleukin (IL)-1b. Application of IL-1 receptor antagonist (IL-1RA) to cocultures attenuated BBC-induced macrophage migration. These data contribute to an understanding of the BBC-mediated activation of the stromal immune response, implicating specific cytokines that are differentially expressed in basal-like microenvironments and suggesting plausible targets for modulating immune responses to BBCs.Introduction: Overall survival of early-stage breast cancer (BC) patients is similar for those who undergo breast conserving therapy (BCT) and mastectomy, however, 10-15% of women undergoing BCT suffer ipsilateral breast tumor recurrence. The risk of recurrence may vary with age or breast cancer subtype. Understanding the gene expression of the cancer-adjacent tissue and/or stromal response to specific tumor subtypes is important for developing clinical strategies to reduce recurrence risk. Methods: We studied gene expression data in cancer-adjacent tissue from 158 BC patients. Complementary in vitro cocultures were used to study cell-cell communication between fibroblasts and specific breast cancer subtypes. Results: Our results suggest that intrinsic tumor subtypes are reflected in histologically normal cancer-adjacent tissue. Gene expression of cancer-adjacent tissues shows that triple negative (Claudin-low or Basal-like tumors) exhibit increased expression of genes involved in inflammation and immune response. While such changes could reflect distinct immune populations present in the microenvironment of different breast cancer subtypes, altered immune response gene expression was also observed in cocultures in the absence of immune cell infiltrates, emphasizing that these inflammatory mediators are secreted by breast-specific cells. In addition, while triple negative BCs are associated with upregulated immune response genes, Luminal breast cancers are more commonly associated with estrogen-response in adjacent tissues. Conclusions: Specific characteristics of BCs are reflected in the surrounding benign tissue. This commonality between tumor and surrounding tissue may underlie second primaries and local recurrences. Biomarkers derived from cancer-adjacent tissue may be helpful in defining personalized surgical strategies or in predicting recurrence risk. reference x sample
2013-11-15 | E-GEOD-52292 | biostudies-arrayexpress
Project description:Intraoperative Electron Radiation Therapy (IOERT) is a therapeutic technique that delivers a single high dose of ionizing radiation (IR) directly to the tumor bed during cancer surgery. The main goal of IOERT is to counteract tumor growth by acting on residual cancer cells in the site at high risk for recurrence as well as to preserve healthy surrounding tissue from the side effects of radiation therapy. The high IR dose used during IOERT treatment induces a strong stress response resulting in the activation of pro- and anti-proliferative cell signaling pathways in both tumor and normal cells. The radiobiology of healthy tissue response to IR is a topic of interest which may contribute to avoid the impairment of normal tissue/organ function and to decrease the risks of secondary cancers. In this study, we examined changes in gene expression in MCF10A breast epithelial cell line exposed to 9Gy and 23Gy high single dose of IR delivered by IOERT. Changes in gene expression in MCF10A breast epithelial cell line exposed to 9Gy and 23Gy high single dose of IR (named MCF10A_9Gy and MCF10A_23Gy respectively), were analyzed as two-color hybridizations using Agilent Technologies whole human genome 4x44K microarrays
2015-07-06 | E-GEOD-65954 | biostudies-arrayexpress
Project description:UFH-001 cells, a newly isolated breast cancer line, have an STR profile that is most similar to that of the control MCF10A cells. Yet, the UFH-001 line is tumor forming with a triple negative phenotype. These cells have a unique transcriptome profile associated numerous breast cancer marker genes. We used microarrays to detail the global programme of gene expression underlying the metastatic behavior of the UFH-001 cells compared to the MCF10A cells.
2018-06-01 | GSE107209 | GEO
Project description:ABSTRACT: Introduction: Basal-like and luminal breast cancers have distinct stromal-epithelial interactions, which likely play a role in progression to invasive cancer. However, little is known about how stromal-epithelial interactions evolve in benign and pre-invasive lesions.Methods: To study epithelial-stroma interactions in basal-like breast cancer progression, we cocultured reduction mammoplasty fibroblasts with the isogenic MCF10 series of cell lines (representing benign/normal, atypical hyperplasia, and ductal carcinoma in situ). We used gene expression microarrays to identify pathways induced by coculture in premalignant cells (MCF10DCIS) compared to normal and benign (MCF10A and MCF10AT1). Relevant pathways were then (1) targeted in vitro and effects on morphogenesis were evaluated and (2) evaluated in vivo for associations with basal-like subtype. Results: Our results show that premalignant MCF10DCIS cells express characteristic gene expression patterns of invasive basal-like microenvironments. Furthermore, while HGF secretion is upregulated (relative to normal, MCF10A levels) when fibroblasts are cocultured with either atypical (MCF10AT cells) or premalignant (MCF10DCIS) cells, only MCF10DCIS cells upregulate the HGF receptor, MET. In 3-dimensional cultures, upregulation of HGF/MET in MCF10DCIS cells induced morphological changes suggestive of invasive potential, and these changes were reversed by antibody-based blocking of HGF signaling. These results are relevant to in vivo progression because high expression of a novel MCF10DCIS-derived HGF signature was correlated with basal-like subtype among invasive cancers, with approximately 86% of basal-like cancers highly expressing the HGF signature. Conclusions: In this study we document coordinated and complementary changes in HGF secretion and MET expression in epithelium and stroma in pre-invasive lesions. These results suggest that targeting stroma-derived HGF signaling in early carcinogenesis may block progression of basal-like precursor lesions.Introduction: In breast cancers, the basal-like subtype has high levels of genomic instability relative to other breast cancer subtypes with many basal-like-specific regions of aberration. There is evidence that this genomic instability extends to smaller scale genomic aberrations as well, as shown by a previously described micro-event in the PTEN gene in the Basal-like SUM149 breast cancer cell line. Methods: We sought to identify if small regions of genomic change exist by using a high density, gene centric Comparative Genomic Hybridizations (CGH) array on both cell lines and primary tumors. A custom Agilent tiling array for CGH (244,000 probes, 200bp tiling resolution) was created to identify small regions of genomic change and was focused on previously identified basal-like-specific, and general cancer genes. Tumor genomic DNA from 94 patients and 2 breast cancer cell lines was labeled and hybridized to these arrays. Aberrations were called using SWITCHdna and the smallest 25% of SWITCHdna-defined genomic segments being called micro-aberrations (<64 contiguous probes, ~ <15kb). Results: Our data showed that primary tumor breast cancer genomes frequently contained areas of small-scale copy number gains and losses, termed micro-aberrations, which are undetectable using lower-density genome-wide platforms. The basal-like subtype exhibited the highest incidence of these events. These micro-aberrations sometimes altered expression of the involved gene as suggested by data from microarray and mRNA-seq studies. We confirmed the presence of the PTEN micro-amplification in SUM149 and by mRNA-seq showed that this resulted in loss of expression of all exons downstream of this event. Micro-aberrations disproportionately affected the 5’ regions of the affected genes, including the promoter region, and a high frequency of micro-aberrations was associated with poor survival outcomes. Conclusion: Using a high probe density, gene-centric aCGH microarray, we present evidence of small-scale genomic aberrations that contribute to gene inactivation, and thus, genomic instability and tumor formation through a mechanism not detected using conventional copy number analyses. reference x sample
2013-07-12 | E-GEOD-43467 | biostudies-arrayexpress