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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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Influence of epithelial cells on adipose connective tissue: a) and b).Hematoxylin Phloxin Safran (HPS) staining for nucleus (purple), cytoplasm (red) and extracellular matrix components (orange); c. Oil red staining: mature adipocytes appeared in red.
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pone-0066284-g002: Influence of epithelial cells on adipose connective tissue: a) and b).Hematoxylin Phloxin Safran (HPS) staining for nucleus (purple), cytoplasm (red) and extracellular matrix components (orange); c. Oil red staining: mature adipocytes appeared in red.

Mentions: The experiment was validated with the results of culture control. Indeed, the 3D adipose model obtained with normal human keratinocytes (NHK) exhibited a balanced, pluristratified, and differentiated epidermis, close to human normal skin (Figure 2). HPS staining showed that fibroblasts and preadipocytes colonized the dermal substrate. The negative Oil Red O staining specific to mature adipocytes showed that no differentiation of preadipocytes into mature adipocytes occurred.


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)

Influence of epithelial cells on adipose connective tissue: a) and b).Hematoxylin Phloxin Safran (HPS) staining for nucleus (purple), cytoplasm (red) and extracellular matrix components (orange); c. Oil red staining: mature adipocytes appeared in red.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0066284-g002: Influence of epithelial cells on adipose connective tissue: a) and b).Hematoxylin Phloxin Safran (HPS) staining for nucleus (purple), cytoplasm (red) and extracellular matrix components (orange); c. Oil red staining: mature adipocytes appeared in red.
Mentions: The experiment was validated with the results of culture control. Indeed, the 3D adipose model obtained with normal human keratinocytes (NHK) exhibited a balanced, pluristratified, and differentiated epidermis, close to human normal skin (Figure 2). HPS staining showed that fibroblasts and preadipocytes colonized the dermal substrate. The negative Oil Red O staining specific to mature adipocytes showed that no differentiation of preadipocytes into mature adipocytes occurred.

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