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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

Development of the adipose skin equivalent.1. Fibroblasts and preadipocytes were seeded on a dermal substrate. 2. After 3 weeks of culture, a fatty equivalent dermis was obtained and keratinocytes (control) or mammary cancer cells (MCF7, MDA-MB-231) or non-cancerous mammary cells (MCF10a) were then seeded on the dermis. 3. After one week of culture, these cells were grown at the air-liquid interface (2 weeks) to obtain the reconstructed fatty skin equivalent. 4. At the end of the experimentation, epithelial cells (n = 3) were separated from the dermis with a thermolysin treatment to extract RNA. The expression of 32 key genes was investigated by qRT-PCR and compared with the expression of cells cultured in normal conditions.
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pone-0066284-g001: Development of the adipose skin equivalent.1. Fibroblasts and preadipocytes were seeded on a dermal substrate. 2. After 3 weeks of culture, a fatty equivalent dermis was obtained and keratinocytes (control) or mammary cancer cells (MCF7, MDA-MB-231) or non-cancerous mammary cells (MCF10a) were then seeded on the dermis. 3. After one week of culture, these cells were grown at the air-liquid interface (2 weeks) to obtain the reconstructed fatty skin equivalent. 4. At the end of the experimentation, epithelial cells (n = 3) were separated from the dermis with a thermolysin treatment to extract RNA. The expression of 32 key genes was investigated by qRT-PCR and compared with the expression of cells cultured in normal conditions.

Mentions: We used a 3D model of skin equivalent [18], [19] (Patent PCT/FR/8800303, 1989) replacing the skin equivalent by an adipose skin equivalent in which breast cancer cell lines were in contact with different cell types such as fibroblasts, preadipocytes and adipocytes (Figure 1). This 3D structure mimicked a breast tumor surrounded by a microenvironment, with breast cell lines being in contact with fibroblasts, preadipocytes and mature adipocytes, and with all their secretions.


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)

Development of the adipose skin equivalent.1. Fibroblasts and preadipocytes were seeded on a dermal substrate. 2. After 3 weeks of culture, a fatty equivalent dermis was obtained and keratinocytes (control) or mammary cancer cells (MCF7, MDA-MB-231) or non-cancerous mammary cells (MCF10a) were then seeded on the dermis. 3. After one week of culture, these cells were grown at the air-liquid interface (2 weeks) to obtain the reconstructed fatty skin equivalent. 4. At the end of the experimentation, epithelial cells (n = 3) were separated from the dermis with a thermolysin treatment to extract RNA. The expression of 32 key genes was investigated by qRT-PCR and compared with the expression of cells cultured in normal conditions.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0066284-g001: Development of the adipose skin equivalent.1. Fibroblasts and preadipocytes were seeded on a dermal substrate. 2. After 3 weeks of culture, a fatty equivalent dermis was obtained and keratinocytes (control) or mammary cancer cells (MCF7, MDA-MB-231) or non-cancerous mammary cells (MCF10a) were then seeded on the dermis. 3. After one week of culture, these cells were grown at the air-liquid interface (2 weeks) to obtain the reconstructed fatty skin equivalent. 4. At the end of the experimentation, epithelial cells (n = 3) were separated from the dermis with a thermolysin treatment to extract RNA. The expression of 32 key genes was investigated by qRT-PCR and compared with the expression of cells cultured in normal conditions.
Mentions: We used a 3D model of skin equivalent [18], [19] (Patent PCT/FR/8800303, 1989) replacing the skin equivalent by an adipose skin equivalent in which breast cancer cell lines were in contact with different cell types such as fibroblasts, preadipocytes and adipocytes (Figure 1). This 3D structure mimicked a breast tumor surrounded by a microenvironment, with breast cell lines being in contact with fibroblasts, preadipocytes and mature adipocytes, and with all their secretions.

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