Dataset Information

Fibroblasts transcriptome altered by breast cell lines

ABSTRACT: Interactions between epithelial cells and their associated stroma, mainly the fibroblasts therein have been implicated in breast malignancy. Our aim was to verify the effect of soluble factors resulting from the co-culture of normal (NAF) or associated breast cancer fibroblasts (CAF) with a normal (MCF-10A) or a metastatic (MDA-MB231) breast epithelial cell line on fibroblast gene expression profiles. Fibroblast primary cultures were established and co-culture of these cell types separated by inserts, which allow the passage of soluble factors, was performed. Total RNA was extracted, amplified and subjected to microarray gene expression profiling using microarrays in which 4,608 ORESTES (open reading frame expressed sequence tags) were spotted. Differentially expressed genes, at a False Discovery Ratio (FDR) less then 0.01 and fold variation greater than 2, were selected. CAF molecular signature was characterized by down regulation of 62% (29/47) of genes as compared to NAF, represented mainly by those related to vesicular transport, cytoskeleton plasticity and cell motility. CAF responded to co-culture with MCF-10A cells by up regulation of 63.5% (89/140) of genes, including those involved with cytoskeleton remodelling, lipid synthesis and members of the PI3K pathway. Contrarywise, MDA-MB231 cells affected the gene expression profile of CAF by down regulation of 65% (102/156) of genes, including those associated to tumor suppression and antiangiogenic potential. Up regulated genes, were mainly implicated with cell cycle progression and proliferation. NAF signature was altered by MDA-MB231 presence resulting in down regulation of suppressor genes, integrins and angiogenic factors, but it was modestly affected by MCF-10A. Keywords: Fibroblasts transcriptome altered by breast cell lines

ORGANISM(S): Homo sapiens

PROVIDER: GSE4708 | GEO | 2006/09/10

SECONDARY ACCESSION(S): PRJNA95589

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Disseminated tumor cells (DTCs) in the bone marrow can be detected in patients with solid tumors early on in disease progression. Via interaction with mesenchymal stromal cells (MSCs) these tumor cells may interfere with hematopoiesis. Using appropriate co-culture models, we investigated whether DTCs can change the bone marrow microenvironment by modulating MSC function with a special emphasis on their chemoattractive activity towards hematopoietic stem and progenitor cells (HSPCs). Human bone marrow derived MSCs as well as an immortalised MSC line (SCP-1) were co-cultured with MCF-7, MDA-MB231 breast carcinoma or MCF-10A non-malignant breast epithelial cells or their conditioned medium. Gene expression analysis of SCP-1 cells cultured with MCF-7 conditioned medium revealed SDF-1/CXCL12 as one of the significantly downregulated genes. Both tumor cell lines caused an inhibited SDF-1 promoter activity in SCP-1 cells, whereby MCF-7 medium decreased it to 77% and MDA-MB231 to 47%. Moreover, the SDF-1 mRNA and protein levels were significantly reduced. As a functional consequence of lower SDF-1 levels, we detected a decreased trans-well migration potential of CD34+ HSPC to MSC/tumor cell co-cultures or conditioned medium. The specificity of this chemokine mediated effect was confirmed by blocking studies with the CXCR4 antagonist AMD3100. Downregulation of SP1 transcription factor and increased miR23a levels in MSCs after contact with tumor cell medium as well as an enhanced TGFb1 expression were identified as potential molecular regulators of SDF-1 activity in MSCs. We propose an additional mechanism by which tumor cells affect the niche environment of HSPCs and therefore negatively impact hematopoiesis. Gene expression of human immortalized mesenchymal stromal cells (SCP-1) was investigated after incubation with conditioned medium of the breast carcinoma cell line MCF-7 for 24, 48, and 72 hours. Three independent experiments were performed at each time.

Dataset Information

Fibroblasts transcriptome altered by breast cell lines

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets