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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

Principal component analysis (PCA) carried out to explore the differences among samples and relationships among genes.The expression of genes by mammary cell lines (MCF7, MDA-MB-231) cultured in control conditions (MCF7_Ctrl, MDA_Ctrl, MCF10a_Ctrl) or cultured in the adipose skin equivalent model (MCF7_3D, MDA_3D, MCF10a_3D) was evaluated using unit variance scaling on gene expression data. On the first principal component, a clear discrimination can be noted between cells cultured in the adipose skin equivalent model versus cells cultured in normal conditions. The second principal component permitted to discriminate the three studied cell lines (MCF7, MDA-MB-231 and MCF10a) among the control group.
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pone-0066284-g004: Principal component analysis (PCA) carried out to explore the differences among samples and relationships among genes.The expression of genes by mammary cell lines (MCF7, MDA-MB-231) cultured in control conditions (MCF7_Ctrl, MDA_Ctrl, MCF10a_Ctrl) or cultured in the adipose skin equivalent model (MCF7_3D, MDA_3D, MCF10a_3D) was evaluated using unit variance scaling on gene expression data. On the first principal component, a clear discrimination can be noted between cells cultured in the adipose skin equivalent model versus cells cultured in normal conditions. The second principal component permitted to discriminate the three studied cell lines (MCF7, MDA-MB-231 and MCF10a) among the control group.

Mentions: The analysis of gene expression was made by principal component analysis (PCA) (Figure 4). The first two principal components account for 63% of the total variance. On the first principal component, a clear discrimination can be seen between cells cultured in the adipose skin equivalent model and those cultured in normal conditions. The second principal component discriminated the three studied cell lines (MCF7, MDA-MB-231 and MCF10a) in the control group. In contrast, PCA showed that the cell lines cultured in the adipose skin equivalent model tended to exhibit the same expression profile. However, two assays of the MDA-MB-231 cells cultured in the 3D model seemed to be at distance from this plot.


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)

Principal component analysis (PCA) carried out to explore the differences among samples and relationships among genes.The expression of genes by mammary cell lines (MCF7, MDA-MB-231) cultured in control conditions (MCF7_Ctrl, MDA_Ctrl, MCF10a_Ctrl) or cultured in the adipose skin equivalent model (MCF7_3D, MDA_3D, MCF10a_3D) was evaluated using unit variance scaling on gene expression data. On the first principal component, a clear discrimination can be noted between cells cultured in the adipose skin equivalent model versus cells cultured in normal conditions. The second principal component permitted to discriminate the three studied cell lines (MCF7, MDA-MB-231 and MCF10a) among the control group.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0066284-g004: Principal component analysis (PCA) carried out to explore the differences among samples and relationships among genes.The expression of genes by mammary cell lines (MCF7, MDA-MB-231) cultured in control conditions (MCF7_Ctrl, MDA_Ctrl, MCF10a_Ctrl) or cultured in the adipose skin equivalent model (MCF7_3D, MDA_3D, MCF10a_3D) was evaluated using unit variance scaling on gene expression data. On the first principal component, a clear discrimination can be noted between cells cultured in the adipose skin equivalent model versus cells cultured in normal conditions. The second principal component permitted to discriminate the three studied cell lines (MCF7, MDA-MB-231 and MCF10a) among the control group.
Mentions: The analysis of gene expression was made by principal component analysis (PCA) (Figure 4). The first two principal components account for 63% of the total variance. On the first principal component, a clear discrimination can be seen between cells cultured in the adipose skin equivalent model and those cultured in normal conditions. The second principal component discriminated the three studied cell lines (MCF7, MDA-MB-231 and MCF10a) in the control group. In contrast, PCA showed that the cell lines cultured in the adipose skin equivalent model tended to exhibit the same expression profile. However, two assays of the MDA-MB-231 cells cultured in the 3D model seemed to be at distance from this plot.

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