Unknown,Transcriptomics,Genomics,Proteomics

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Molecular Characterization of Breast Carcinoma Associate fibroblasts

ABSTRACT: Normal breast fibroblasts, breast cancer associated fibroblasts, fibroblasts taken at least 2cm from cancer margins and femur-derived human mesenchymal stem cells were profiled for comparative purposes Ex vivo cultured primary cells of different anatomical origin were expression profiled under low serum conditions: cancer-associated fibroblasts, fibroblasts from a distance of at least 2cm from the cancers' edge, fibroblasts from cancer-free breasts and mesenchymal stromal cells from the marrow of femurs. Biological Replicates= 46. Technical Replicates= 17

ORGANISM(S): Homo sapiens

SUBMITTER: Mark Basik

PROVIDER: E-GEOD-29270 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:The tissue stroma plays a major role in tumors natural history. Important programs for tumor progression such as epithelial mesenchymal transition are not activated as cell-autonomous processes but under the conditions of cross-talk between tumor and stroma. Adipose tissue is a major component of the stroma and, because of their extended half-life, adipocytes are witnesses of tissue exposures. This study compares breast fat in women with breast tumors to those in healthy women to try to define a signature that could be translated into biomarkers for cancer and / or cancer risk. In the tumor-bearing breasts, we sampled adipose tissues adjacent to or distant from the tumor. Parameters studied include: adipocytes size and density; immune cells infiltration, vascularization, functional excretion and gene expression. Adipose tissues from tumor-bearing breasts whether adjacent to or distant from the tumor, did not differ from each other by any of these parameters. By contrast, when compared to adipose tissues from tumor-free breasts, tissues from tumor-bearing breasts displayed functional characteristics pointing to some sort of \\"activation\\". They have the capacity to excrete twice as much of interleukin 8 (p=0.001) and they differentially express a set of around 200 genes, at a threshold of p-value 0.001, of which many belong to inflammation mediated by chemokine and cytokine signaling and integrin signaling pathways. The presence of mast cells appears as a strong predictor of IL-8 secretion capacity (Log2 scale p = 0.002). Therefore, breast fat tissues from breast cancer patients have distinct functional and expression profiles. Although a dialogue effect with the tumor cannot be ruled out, it is also possible that this status is individually defined thus determining the constitutive permissiveness of the tissue for the development of cancer. The activation of pathways that was observed could potentially be translated into biomarkers or therapeutic targets. This transcriptomic analysis has been performed on two types of samples at short and long distances from the tumour in comparison with samples from normal tissues on Illumina beadarrays.

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Molecular Characterization of Breast Carcinoma Associate fibroblasts

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