Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA151155 | ENA |
REPOSITORIES: ENA
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Project description:One of the barriers for breast cancer prevention and treatment is our poor understanding of the dynamic cellular shifts that naturally occur within the breast and how these changes contribute to tumour initiation. In this study we report the use of single cell RNA sequencing (scRNAseq) to compile a Human Breast Cell Atlas (HBCA) assembled from 55 donors that had undergone reduction mammoplasties or risk reduction mammoplasties. The data from more than 800,000 cells identified 41 cell subclusters distributed across the epithelial, immune, and stromal compartments. We found that the contribution of these different clusters varied according to the natural history of the tissue. Breast cancer risk modulating factors such as age, parity, and germline mutation affected the homeostatic cellular state of the breast in different ways however, none of the changes observed were restricted to any one cell type. Remarkably, we also found that immune cells from BRCA1/2 carriers had a distinct gene expression signature indicative of potential immune exhaustion which was validated by immunohistochemistry. This suggests that immune escape mechanisms could manifest in non-cancerous tissues during very early stages of tumour initiation. Therefore, the Atlas presented here provides the research community with a rich resource that can be used as a reference for studies on the origins of breast cancer which could inform novel approaches for early detection and prevention.
2024-04-03 | E-MTAB-13664 | biostudies-arrayexpress
Project description:High-grade serous carcinoma has a poor prognosis, owing primarily to its early dissemination throughout the abdominal cavity. Genomic and proteomic approaches have provided snapshots of the proteogenomics of ovarian cancer, but a systematic examination of both the tumour and stromal compartments is critical in understanding ovarian cancer metastasis. We developed a label- free proteomic workflow to analyse as few as 5,000 formalin-fixed, paraffin-embedded cells microdissected from each compartment. The tumour proteome was stable during progression from in situ lesions to metastatic disease; however, the metastasis-associated stroma was characterized by a highly conserved proteomic signature, prominently including the methyltransferase nicotinamide N-methyltransferase (NNMT) and several of the proteins that it regulates. Stromal NNMT expression was necessary and sufficient for functional aspects of the cancer-associated fibroblast (CAF) phenotype, including the expression of CAF markers and the secretion of cytokines and oncogenic extracellular matrix. Stromal NNMT expression supported ovarian cancer migration, proliferation and in vivo growth and metastasis. Expression of NNMT in CAFs led to depletion of S-adenosyl methionine and reduction in histone methylation associated with widespread gene- expression changes in the tumour stroma. This work supports the use of ultra-low-input proteomics to identify candidate drivers of disease phenotypes. NNMT is a central, metabolic regulator of CAF differentiation and cancer progression in the stroma that may be therapeutically targeted.
2019-04-18 | PXD006396 | Pride
Project description:The ability of primary tumour cells to invade and metastasise is responsible for over 90% of cancer patient deaths. During tumour growth and progression, cancer cells secrete factors that recruit and reprogram otherwise healthy cells to facilitate the formation of a favourable tumour microenvironment. Here, we have investigated how breast cancer cells convert normal mesenchymal stromal cells (MSCs) into tumour-associated MSCs (TA-MSCs) using unbiased global approaches. We compared the secretomes produced by non-invasive MCF-7 cells with invasive MDA-MB-231 cells, and identified extracellular matrix and exosome components associated with invasion. We then treated MSCs cultured in fully-defined, synthetic 3D hydrogels with invasive/non-invasive cancer secretomes and analysed their responses by kinase activity profiling and RNA sequencing, which led us to identify an invasion-associated signature of MSC conversion. Finally, we investigated whether there is an organ-specific metastasis-associated reprogramming of MSCs, and found that breast cancer cells from different metastatic sites have different secretome profiles that induce reprogramming of MSCs. These data describe at a systems-level how breast cancer cells with different invasion and metastatic abilities secrete molecules that activate MSCs and convert them into TA-MSCs.
2019-05-27 | PXD010467 | Pride
Project description:With this experiment, we aimed to decipher the epigenetic changes occuring during tumour progression in a model of basal-like breast cancer, based on immortalized mammary epithelial cells (IMEC). The tumorigenic IMEC, xenograft-derived and metastasis-derived cells were used for the analysis
2024-02-02 | GSE211606 | GEO
Project description:Analysis of differentially expressed genes from dissected whole tissue and laser capture microdissected colorectal cancer tissue samples The analysis, in colorectal cancer tissues, of compartmental and whole tissue expression profiles as well as the significantly active pathways that were differentially deregulated between the epithelial and stromal compartments when compared alongside that of whole tissue dissection
2011-08-10 | GSE31279 | GEO
Project description:With this experiment, we aimed to decipher the changes in chromatin accessibility during tumour progression in a model of basal-like breast cancer, based on immortalized mammary epithelial cells (IMEC). The tumorigenic IMEC, xenograft-derived and metastasis-derived cells were used for the analysis
2024-02-02 | GSE211605 | GEO
Project description:Analysis of differentially expressed genes from dissected whole tissue and laser capture microdissected colorectal cancer tissue samples The analysis, in colorectal cancer tissues, of compartmental and whole tissue expression profiles as well as the significantly active pathways that were differentially deregulated between the epithelial and stromal compartments when compared alongside that of whole tissue dissection Comparison of tumor epithelium vs normal epithelium; tumor stroma vs normal stroma and tumor whole tissue vs normal whole tissue
2011-08-09 | E-GEOD-31279 | biostudies-arrayexpress
Project description:Background: Epithelial-stromal crosstalk plays a critical role in invasive breast cancer (IBC) pathogenesis; however, little is known on a systems level about how epithelial-stromal interactions evolve during carcinogenesis. Results: We develop a framework for building genome-wide epithelial-stromal co-expression networks composed of pairwise co-expression relationships between mRNA levels of genes expressed in the epithelium and stroma across a population of patients. We apply this method to laser capture micro-dissection expression profiling datasets in the setting of breast carcinogenesis. Our analysis shows that epithelial-stromal co-expression networks undergo extensive re-wiring during carcinogenesis, with the emergence of distinct network hubs in normal breast, ER-positive IBC, and ER-negative IBC, and the emergence of distinct patterns of functional network enrichment. In contrast to normal breast, the strongest epithelial-stromal co-expression relationships in IBC mostly represent self-loops, in which the same gene is co-expressed in epithelial and stromal regions. We validate this observation using an independent laser capture micro-dissection dataset and confirm that self-loop interactions are significantly increased in cancer by performing computational image analysis of epithelial and stromal protein expression using images from the Human Protein Atlas. Conclusions: Epithelial-stromal co-expression network analysis represents a new approach for systems-level analyses of spatially-localized transcriptomic data. The analysis provides new biological insights into the re-wiring of epithelial-stromal co-expression networks and the emergence of epithelial-stromal co-expression self-loops in breast cancer. The approach may facilitate the development of new diagnostics and therapeutics targeting epithelial-stromal interactions in cancer. 36 flash-frozen human primary breast cancer samples were subjected to laser capture microdissection to separately isolate matched tumor epithelial and tumor-associated stromal components. RNA was isolated, subjected to 2 rounds of amplification, and hybridized on Agilent 4x44K microarrays along with a common reference (single round-amplified commercially obtained Universal Human Reference RNA) in a dyeswap design. For two samples of tumor-associated stroma, a second technical replicate was performed. Samples were labelled as ER-positive based on ESR1 gene expression levels in the tumor epithelium, using univariate Gaussian mixture model-based clustering via the mclust package in R.
2015-05-12 | E-GEOD-68744 | biostudies-arrayexpress
Project description:Epithelial-Mesenchymal Transition (EMT) is an important process during normal development, but also co-opted by various cancer cells to enable them to invade and form metastases at distant sites. In this study, we examinated changes in gene expression during EMT in breast cancer using primary culture named BCpc. Changes in gene expression in primary cells from breast tumour specimen (named BCpc) were analyzed as two-color hybridizations using Agilent Technologies whole human genome 4x44K microarrays
2014-06-02 | E-GEOD-53175 | biostudies-arrayexpress
Project description:With this experiment, we aimed to decipher the changes in gene expression during tumour progression in a model of basal-like breast cancer, based on immortalized mammary epithelial cells (IMEC). The tumorigenic IMEC, xenograft-derived and metastasis-derived cells were used for the total RNA-seq analysis.
2024-02-02 | GSE211608 | GEO