Beige adipocytes contribute to breast cancer progression

GANTOV, MARIANA; PAGNOTTA, PRISCILA; LOTUFO, CECILIA; RINDONE, GUSTAVO; RIERA, MARIA; CALVO, JUAN; TONEATTO, JUDITH

ONCOLOGY REPORTS

SPANDIDOS PUBL LTD

Año: 2020

1021-335X

Abstract. Adipocytes are the main stromal cells in themammary microenvironment, and crosstalk between adipo‑cytes and breast cancer cells may play a critical and importantrole in cancer maintenance and progression. Tumor‑induceddifferentiation to beige/brown adipose tissue is an importantcontribution to the hypermetabolic state of breast cancer.However, the effect of epithelial cell‑beige adipocyte commu‑nication on tumor progression remains unclear. To contributeto the understanding of this phenomenon, we characterizedcomponents present in conditioned media (CM) from beige adipocytes (BAs) or white adipocytes (WAs), and evaluatedthe effects of BA‑ and WA‑CM on both adhesion and migrationof tumor (LM3, 4T1 and MC4‑L1) and non‑tumor (NMuMG)mouse mammary epithelial cell lines. Additionally, weanalyzed the expression of ObR, CD44, vimentin, MMP‑9,MCT1 and LDH in tumor and non‑tumor mouse mammaryepithelial cell lines incubated with BA‑CM, WA‑CM orCtrol‑CM (control conditioned media). 3T3‑L1 preadipocytesdifferentiated into beige adipocytes upon PPARγ activation(rosiglitazone) displaying characteristics that morphologicallyresembled brown/beige adipocytes. Levels of UCP1, CIDEA,GLUT4, leptin, MCT4 and FABP4 were increased, whileadiponectin, caveolin 1 and perilipin 1 levels were decreasedin BAs with respect to WAs. Tumor cell lines revealed lowercell adhesion and increased cell migration after incubationwith BA‑ and WA‑CM vs. Ctrol‑CM. ObR and MMP‑9 inMC4‑L1 cells were significantly increased after incubationwith BA‑CM vs. WA‑ and Ctrol‑CM. In addition, MC4‑L1and LM3 cells significantly increased their migration in thepresence of BAs, suggesting that new signals originatingfrom the crosstalk between BAs and tumor cells, could beresponsible for this change. Our results indicate that beigeadipocytes are able to regulate the behavior of both tumor andnon‑tumor mouse mammary epithelial cells, favoring tumorprogression.