Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Molecular profiling of functional interactions between pre-osteoblastic and breast carcinoma cells

ABSTRACT: The relationships between cancer cells and the microenvironment play a critical role in cancer growth and development. The bone stroma consists of mesenchymal stem cells (MSCs) and mature osteoblasts that promote cancer growth. Yet it is not completely understood what are the molecular processes guiding cancer cells progression to the bone. In this study, a co-culture assay and subsequent gene profiling arrays were used to compare the gene expression profile of a pre-osteoblastic cell line (MBA-15) with that of a mammary adenocarcinoma (DA3) cells. Following co-culture, cells were separated by magnetic beads based on the expression of CD326 antigen. RNA was purified and hybridized on gene expression array. The gene expression pattern changes were followed by qRT-PCR. We demonstrate that co-cultured DA3 cells express elevated levels of genes that regulate growth and responses to both hormonal stimulus and wounding, as well as reduced expression of genes related to lipid metabolism. Also, co-cultured pre-osteoblastic cells showed reduced expression of cell-junction genes. The study presents a simplified model system, composed of pre-osteoblastic and mammary cancer cells, that potentially mimics the molecular interactions in the tumor microenvironment which contribute to tumor-progression. Gene expression was studied in 2 mouse cell lines: MBA-15, a pre-osteoblastic stromal cell line, and DA3, a mammary adenocarcinomal cell line. The interaction between these 2 cell lines was also analysed by gene expression. The experiment was performed in duplicates (see Date in the Sample characteristics field).

ORGANISM(S): Mus musculus

SUBMITTER: Metsada Pasmanik-Chor

PROVIDER: E-GEOD-34529 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Molecular profiling of functional interactions between pre-osteoblastic and breast carcinoma cells.

Glait-Santar Chen C Pasmanik-Chor Metsada M Oron-Karni Varda V Benayahu Dafna D

Genes to cells : devoted to molecular & cellular mechanisms 20120302 4

The relationships between cancer cells and the microenvironment play a critical role in cancer growth and development. The bone stroma consists of mesenchymal stem cells and mature osteoblasts that promote cancer growth. Yet it is not completely understood what are the molecular processes guiding cancer cells progression to the bone. In this study, a coculture assay and subsequent gene profiling arrays were used to compare the gene expression profile of a pre-osteoblastic (PO) cell line (MBA-15) ...[more]

PMID: 22380569

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Project description:Background: The differential expression pattern of microRNAs (miRNAs) during mammary gland development might provide insights into their role in regulating the homeostasis of the breast epithelium. Our aim was to analyse these regulatory functions by deriving a comprehensive tissue-specific combined miRNA and mRNA expression profile of post-natal mouse mammary gland development. We measured the expression of 318 individual murine miRNAs by bead-based flow-cytometric profiling of whole mouse mammary glands throughout a 16-point developmental time course, including juvenile, puberty, mature virgin, gestation, lactation, and involution stages. In parallel whole-genome mRNA expression data were obtained. Results: One third (n = 102) of all murine miRNAs analysed were present during mammary gland development. MicroRNAs were represented in seven temporally co-expressed clusters, which were enriched for both miRNAs belonging to the same family and breast cancer-associated miRNAs. Global miRNA and mRNA expression was significantly reduced during lactation and the early stages of involution after weaning. For most detected miRNA families we did not observe systematic changes in the expression of predicted targets. For miRNA families whose targets did show significant changes, we observed inverse patterns of miRNA and target expression. The datasets are made publicly available and the combined expression profiles represent an important community resource for mammary gland biology research. Conclusions: MicroRNAs were expressed in co-regulated clusters during mammary gland development. Breast cancer-associated miRNAs were significantly enriched in these clusters. The mechanism and functional consequences of this miRNA co-regulation and its correlation with mRNA expression provide new avenues for research into mammary gland biology and generates candidates for functional validation. Developmental time course over 17 time points with 2-3 independent biological replicates per time point and four pairs of technical replicates, 48 samples in total

Project description:Molecular mechanisms of the cancer cells-macrophages interactions growing in vitro conditions as a co-culture. The five canine mammary cancer cell lines were cultured with monocytes sorted from the canine blood for 72hrs. Then, the cancer cells and macrophages were sorted and the gene expression analysis was conducted. The control for each co-cultured cell line was the same cell line growing as a single culture, whereas the control for the macrophages growing in a co-culture conditions were macrophages growing as a single culture. Solid tumors are comprised of various cells, like cancer cells, resident stromal cells, migratory hemopoietic cells and so on. These cells regulate tumor growth and metastasis. Macrophages are probably the most important element of the interactions within the tumor microenvironment. However, the molecular mechanism how the tumor environment can educate tumor-associated macrophages (TAMs) toward a tumor-promoting phenotype still remains unknown. Moreover, there are no information how the presence of macrophages change the cancer cells phenotype. Exploring the underlying molecular mechanisms of these phenomena was the aim of this study. Solid tumors are comprised of various cells, like cancer cells, resident stromal cells, migratory hemopoietic cells and so on. These cells regulate tumor growth and metastasis. Macrophages are probably the most important element of the interactions within the tumor microenvironment. However, the molecular mechanism how the tumor environment can educate tumor-associated macrophages (TAMs) toward a tumor-promoting phenotype still remains unknown. Moreover, there are no information how the presence of macrophages change the cancer cells phenotype. Exploring the underlying molecular mechanisms of these phenomena was the aim of this study. Dye-swap experiment, each cell line growing in the co-culture conditions was compared to the same cell line growing as a single culture, macrophages growing in the co-culture conditions were compared to the macrophages growing as the single culture.

Project description:Background: The differential expression pattern of microRNAs (miRNAs) during mammary gland development might provide insights into their role in regulating the homeostasis of the breast epithelium. Our aim was to analyse these regulatory functions by deriving a comprehensive tissue-specific combined miRNA and mRNA expression profile of post-natal mouse mammary gland development. We measured the expression of 318 individual murine miRNAs by bead-based flow-cytometric profiling of whole mouse mammary glands throughout a 16-point developmental time course, including juvenile, puberty, mature virgin, gestation, lactation, and involution stages. In parallel whole-genome mRNA expression data were obtained. Results: One third (n = 102) of all murine miRNAs analysed were present during mammary gland development. MicroRNAs were represented in seven temporally co-expressed clusters, which were enriched for both miRNAs belonging to the same family and breast cancer-associated miRNAs. Global miRNA and mRNA expression was significantly reduced during lactation and the early stages of involution after weaning. For most detected miRNA families we did not observe systematic changes in the expression of predicted targets. For miRNA families whose targets did show significant changes, we observed inverse patterns of miRNA and target expression. The datasets are made publicly available and the combined expression profiles represent an important community resource for mammary gland biology research. Conclusions: MicroRNAs were expressed in co-regulated clusters during mammary gland development. Breast cancer-associated miRNAs were significantly enriched in these clusters. The mechanism and functional consequences of this miRNA co-regulation and its correlation with mRNA expression provide new avenues for research into mammary gland biology and generates candidates for functional validation. This SuperSeries is composed of the following subset Series: GSE15054: Characterisation of microRNA expression in post-natal mouse mammary gland development [gene] GSE15055: Characterisation of microRNA expression in post-natal mouse mammary gland development [miRNA] Refer to individual Series

Dataset Information

Molecular profiling of functional interactions between pre-osteoblastic and breast carcinoma cells

Publications

Molecular profiling of functional interactions between pre-osteoblastic and breast carcinoma cells.

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