Abstract
The relationship between obesity and breast cancer (BC) has focused on serum factors. However, the mammary gland contains adipose tissue (AT) which may enable the crosstalk between adipocytes and tumor cells contributing to tumor macrophage recruitment. We hypothesize that the breast AT (bAT) is inflamed in obese females and plays a major role in breast cancer development. The effects of this interplay on macrophage chemotaxis were examined in vitro, using co-cultures of mouse macrophages, mammary tumor cells and adipocytes. Macrophages were exposed to the adipocyte and tumor paracrine factors leptin, CCL2 and lauric acid (alone or in combinations). In cell supernatants Luminex identified additional molecules with chemotactic and other pro-tumor functions. Focus on the adipokine leptin, which has been shown to have a central role in breast cancer pathogenesis, indicated it modulates macrophage phenotypes and functions. In vivo experiments demonstrate that mammary tumors from obese mice are larger and that bAT from obese tumor-bearers contains higher numbers of macrophages/CLS and hypertrophic adipocytes than bAT from lean tumor-bearers, thus confirming it is more inflamed. Also, bAT distal from the tumor is more inflamed in obese than in lean mice. Our results reveal that bAT plays a role in breast cancer development in obesity.
| Original language | English |
|---|---|
| Pages (from-to) | 143-178 |
| Number of pages | 36 |
| Journal | Cancers |
| Volume | 7 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 15 2015 |
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Keywords
- Adipocytes
- Breast adipose tissue
- Breast cancer
- Breast tumor cells
- Chemotaxis
- Diet-induced obesity
- Inflammation
- Macrophages
- Obesity
- Tumor microenvironment
- Tumor progression
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Paracrine interactions between adipocytes and tumor cells recruit and modify macrophages to the mammary tumor microenvironment : the role of obesity and inflammation in breast adipose tissue. / Santander, Ana M.; Lopez-Ocejo, Omar; Casas, Olivia; Agostini, Thais; Sanchez, Lidia; Lamas-Basulto, Eduardo; Carrio, Roberto; Cleary, Margot P.; Gonzalez-Perez, Ruben R.; Torroella-Kouri, Marta.
In: Cancers, Vol. 7, No. 1, 15.01.2015, p. 143-178.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Paracrine interactions between adipocytes and tumor cells recruit and modify macrophages to the mammary tumor microenvironment
T2 - the role of obesity and inflammation in breast adipose tissue
AU - Santander, Ana M.
AU - Lopez-Ocejo, Omar
AU - Casas, Olivia
AU - Agostini, Thais
AU - Sanchez, Lidia
AU - Lamas-Basulto, Eduardo
AU - Carrio, Roberto
AU - Cleary, Margot P.
AU - Gonzalez-Perez, Ruben R.
AU - Torroella-Kouri, Marta
PY - 2015/1/15
Y1 - 2015/1/15
N2 - The relationship between obesity and breast cancer (BC) has focused on serum factors. However, the mammary gland contains adipose tissue (AT) which may enable the crosstalk between adipocytes and tumor cells contributing to tumor macrophage recruitment. We hypothesize that the breast AT (bAT) is inflamed in obese females and plays a major role in breast cancer development. The effects of this interplay on macrophage chemotaxis were examined in vitro, using co-cultures of mouse macrophages, mammary tumor cells and adipocytes. Macrophages were exposed to the adipocyte and tumor paracrine factors leptin, CCL2 and lauric acid (alone or in combinations). In cell supernatants Luminex identified additional molecules with chemotactic and other pro-tumor functions. Focus on the adipokine leptin, which has been shown to have a central role in breast cancer pathogenesis, indicated it modulates macrophage phenotypes and functions. In vivo experiments demonstrate that mammary tumors from obese mice are larger and that bAT from obese tumor-bearers contains higher numbers of macrophages/CLS and hypertrophic adipocytes than bAT from lean tumor-bearers, thus confirming it is more inflamed. Also, bAT distal from the tumor is more inflamed in obese than in lean mice. Our results reveal that bAT plays a role in breast cancer development in obesity.
AB - The relationship between obesity and breast cancer (BC) has focused on serum factors. However, the mammary gland contains adipose tissue (AT) which may enable the crosstalk between adipocytes and tumor cells contributing to tumor macrophage recruitment. We hypothesize that the breast AT (bAT) is inflamed in obese females and plays a major role in breast cancer development. The effects of this interplay on macrophage chemotaxis were examined in vitro, using co-cultures of mouse macrophages, mammary tumor cells and adipocytes. Macrophages were exposed to the adipocyte and tumor paracrine factors leptin, CCL2 and lauric acid (alone or in combinations). In cell supernatants Luminex identified additional molecules with chemotactic and other pro-tumor functions. Focus on the adipokine leptin, which has been shown to have a central role in breast cancer pathogenesis, indicated it modulates macrophage phenotypes and functions. In vivo experiments demonstrate that mammary tumors from obese mice are larger and that bAT from obese tumor-bearers contains higher numbers of macrophages/CLS and hypertrophic adipocytes than bAT from lean tumor-bearers, thus confirming it is more inflamed. Also, bAT distal from the tumor is more inflamed in obese than in lean mice. Our results reveal that bAT plays a role in breast cancer development in obesity.
KW - Adipocytes
KW - Breast adipose tissue
KW - Breast cancer
KW - Breast tumor cells
KW - Chemotaxis
KW - Diet-induced obesity
KW - Inflammation
KW - Macrophages
KW - Obesity
KW - Tumor microenvironment
KW - Tumor progression
UR - http://www.scopus.com/inward/record.url?scp=84922328217&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84922328217&partnerID=8YFLogxK
U2 - 10.3390/cancers7010143
DO - 10.3390/cancers7010143
M3 - Article
AN - SCOPUS:84922328217
VL - 7
SP - 143
EP - 178
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 1
ER -