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Oncology Reports
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Article . 2020
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Oncology Reports
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Oncology Reports
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Beige adipocytes contribute to breast cancer progression

Authors: Gantov, Mariana; Pagnotta, Priscila Ayelén; Lotufo, Cecilia Maricel; Rindone, Gustavo Marcelo; Riera, Maria Fernanda; Calvo, Juan Carlos; Toneatto, Judith;

Beige adipocytes contribute to breast cancer progression

Abstract

Adipocytes are the main stromal cells in the mammary microenvironment, and crosstalk between adipocytes and breast cancer cells may play a critical and important role in cancer maintenance and progression. Tumor‑induced differentiation to beige/brown adipose tissue is an important contribution to the hypermetabolic state of breast cancer. However, the effect of epithelial cell‑beige adipocyte communication on tumor progression remains unclear. To contribute to the understanding of this phenomenon, we characterized components present in conditioned media (CM) from beige adipocytes (BAs) or white adipocytes (WAs), and evaluated the effects of BA‑ and WA‑CM on both adhesion and migration of tumor (LM3, 4T1 and MC4‑L1) and non‑tumor (NMuMG) mouse mammary epithelial cell lines. Additionally, we analyzed the expression of ObR, CD44, vimentin, MMP‑9, MCT1 and LDH in tumor and non‑tumor mouse mammary epithelial cell lines incubated with BA‑CM, WA‑CM or Ctrol‑CM (control conditioned media). 3T3‑L1 preadipocytes differentiated into beige adipocytes upon PPARγ activation (rosiglitazone) displaying characteristics that morphologically resembled brown/beige adipocytes. Levels of UCP1, CIDEA, GLUT4, leptin, MCT4 and FABP4 were increased, while adiponectin, caveolin 1 and perilipin 1 levels were decreased in BAs with respect to WAs. Tumor cell lines revealed lower cell adhesion and increased cell migration after incubation with BA‑ and WA‑CM vs. Ctrol‑CM. ObR and MMP‑9 in MC4‑L1 cells were significantly increased after incubation with BA‑CM vs. WA‑ and Ctrol‑CM. In addition, MC4‑L1 and LM3 cells significantly increased their migration in the presence of BAs, suggesting that new signals originating from the crosstalk between BAs and tumor cells, could be responsible for this change. Our results indicate that beige adipocytes are able to regulate the behavior of both tumor and non‑tumor mouse mammary epithelial cells, favoring tumor progression.

Keywords

Adipocytes, White, Breast Neoplasms, BEIGE ADIPOCYTES, WHITE ADIPOCYTES, Rosiglitazone, Mice, Mammary Glands, Animal, BREAST CANCER, Cell Movement, 3T3-L1 Cells, Cell Line, Tumor, https://purl.org/becyt/ford/3.1, Cell Adhesion, Tumor Microenvironment, Animals, Humans, https://purl.org/becyt/ford/3, Adipocytes, Beige, TUMOR PROGRESSION, Mammary Neoplasms, Experimental, SOLUBLE FACTORS, Cell Differentiation, PPAR gamma, Culture Media, Conditioned, Disease Progression, Female, TUMOR MICROENVIRONMENT

  • BIP!
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    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    16
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Average
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
16
Top 10%
Average
Top 10%
Green
bronze