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Reciprocal interactions between breast tumor and its adipose microenvironment based on a 3D adipose equivalent model.

Delort L, Lequeux C, Dubois V, Dubouloz A, Billard H, Mojallal A, Damour O, Vasson MP, Caldefie-Chézet F - PLoS ONE (2013)

Bottom Line: These mimicked a breast tumor in contact with an adipose microenvironment and allowed monitoring of the interactions between the cells.The differentiation of preadipocytes into adipocytes was greater when they were in contact with the breast cancer cell lines.The contact of breast cancer cell lines with the microenvironment completely modified their transcriptional programs by increasing the expression of genes involved in cell proliferation (cyclinD1, MAPK), angiogenesis (MMP9, VEGF) and hormonal pathways (ESR1, IL6).

View Article: PubMed Central - PubMed

Affiliation: Clermont Université, Université d'Auvergne, UFR Pharmacie, Laboratoire SVFp, Clermont-Ferrand, France. laetitia.delort@udamail.fr

ABSTRACT
Breast cancer has become the most common cancer among women in industrialized countries. Obesity is well established as a risk factor, in particular owing to the attendant secretion of the entities called adipokines; there is growing evidence for a role of cells and factors present in the mammary tumor microenvironment such as fibroblasts, preadipocytes, adipocytes and their secretions. To study how the microenvironment influences breast cancer growth, we developed a novel tridimensional adipose model epithelialized with normal human keratinocytes or with breast cancer cell lines. These mimicked a breast tumor in contact with an adipose microenvironment and allowed monitoring of the interactions between the cells. Leptin and adiponectin, two major adipokines, and their respective receptors, ObRt and AdipoR1, were expressed in the model, but not the second adiponectin receptor, AdipoR2. The differentiation of preadipocytes into adipocytes was greater when they were in contact with the breast cancer cell lines. The contact of breast cancer cell lines with the microenvironment completely modified their transcriptional programs by increasing the expression of genes involved in cell proliferation (cyclinD1, MAPK), angiogenesis (MMP9, VEGF) and hormonal pathways (ESR1, IL6). This tridimensional adipose model provides new insights into the interactions between breast cancer cells and their adipose microenvironment, and provides a tool to develop new drugs for the treatment of both cancer and obesity.

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Related in: MedlinePlus

Hierarchical cluster analysis of the genes differentially expressed between the three studied mammary cell lines (MCF7, MDA-MB-231, MCF10a) in control conditions (Ctrl) or cultured in the adipose skin adipose model (3D).Expression blocks were formed, the red block being more expressed than the green block.
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pone-0066284-g005: Hierarchical cluster analysis of the genes differentially expressed between the three studied mammary cell lines (MCF7, MDA-MB-231, MCF10a) in control conditions (Ctrl) or cultured in the adipose skin adipose model (3D).Expression blocks were formed, the red block being more expressed than the green block.

Mentions: Hierarchical cluster analysis (HCA) (Figure 5) allowed us to evaluate the low to high expression of each gene in each control and 3D assay. It discriminated cells cultured in control conditions and cells cultured in the 3D model, except for one assay of MDA-MB-231 cultured in control condition. This representation led to the formation of expression blocks, red and green, of which the former was more strongly expressed.


Reciprocal interactions between breast tumor and its adipose microenvironment based on a 3D adipose equivalent model.

Delort L, Lequeux C, Dubois V, Dubouloz A, Billard H, Mojallal A, Damour O, Vasson MP, Caldefie-Chézet F - PLoS ONE (2013)

Hierarchical cluster analysis of the genes differentially expressed between the three studied mammary cell lines (MCF7, MDA-MB-231, MCF10a) in control conditions (Ctrl) or cultured in the adipose skin adipose model (3D).Expression blocks were formed, the red block being more expressed than the green block.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3672201&req=5

pone-0066284-g005: Hierarchical cluster analysis of the genes differentially expressed between the three studied mammary cell lines (MCF7, MDA-MB-231, MCF10a) in control conditions (Ctrl) or cultured in the adipose skin adipose model (3D).Expression blocks were formed, the red block being more expressed than the green block.
Mentions: Hierarchical cluster analysis (HCA) (Figure 5) allowed us to evaluate the low to high expression of each gene in each control and 3D assay. It discriminated cells cultured in control conditions and cells cultured in the 3D model, except for one assay of MDA-MB-231 cultured in control condition. This representation led to the formation of expression blocks, red and green, of which the former was more strongly expressed.

Bottom Line: These mimicked a breast tumor in contact with an adipose microenvironment and allowed monitoring of the interactions between the cells.The differentiation of preadipocytes into adipocytes was greater when they were in contact with the breast cancer cell lines.The contact of breast cancer cell lines with the microenvironment completely modified their transcriptional programs by increasing the expression of genes involved in cell proliferation (cyclinD1, MAPK), angiogenesis (MMP9, VEGF) and hormonal pathways (ESR1, IL6).

View Article: PubMed Central - PubMed

Affiliation: Clermont Université, Université d'Auvergne, UFR Pharmacie, Laboratoire SVFp, Clermont-Ferrand, France. laetitia.delort@udamail.fr

ABSTRACT
Breast cancer has become the most common cancer among women in industrialized countries. Obesity is well established as a risk factor, in particular owing to the attendant secretion of the entities called adipokines; there is growing evidence for a role of cells and factors present in the mammary tumor microenvironment such as fibroblasts, preadipocytes, adipocytes and their secretions. To study how the microenvironment influences breast cancer growth, we developed a novel tridimensional adipose model epithelialized with normal human keratinocytes or with breast cancer cell lines. These mimicked a breast tumor in contact with an adipose microenvironment and allowed monitoring of the interactions between the cells. Leptin and adiponectin, two major adipokines, and their respective receptors, ObRt and AdipoR1, were expressed in the model, but not the second adiponectin receptor, AdipoR2. The differentiation of preadipocytes into adipocytes was greater when they were in contact with the breast cancer cell lines. The contact of breast cancer cell lines with the microenvironment completely modified their transcriptional programs by increasing the expression of genes involved in cell proliferation (cyclinD1, MAPK), angiogenesis (MMP9, VEGF) and hormonal pathways (ESR1, IL6). This tridimensional adipose model provides new insights into the interactions between breast cancer cells and their adipose microenvironment, and provides a tool to develop new drugs for the treatment of both cancer and obesity.

Show MeSH
Related in: MedlinePlus