Differentiation of 3T3-L1 preadipocytes into beige adipocytes regulate mammary tumor cells behavior

Mariana Gantov¹, Priscila Pagnotta¹,3, Cecilia Lotufo¹, Gustavo Rindone², Maria Fernanda Riera², Juan Carlos Calvo¹,3, Judith Toneatto¹

We previously demonstrated a metabolic and phenotypic switch of 3T3-L1 white adipocytes into beige adipocytes (browning) when presented to soluble factors secreted by mammary epithelial cancer cells. Browning of adipose tissue is an important contribution to the hypermetabolic state of breast cancer. The factors and signaling pathways responsible for the browning process are unknown, as well as the role of beige adipocytes could have on the tumor. Thus, the aim of study was to obtain insight into the effect of epithelial cell-beige adipocyte communication on tumor progression.We characterized components present in conditioned media (CMs) from beige adipocytes (BA) or white adipocytes (WA) achieved upon differentiation of 3T3-L1 preadipocytes, and evaluated the effects of BA-CMs and WA-CMs on both adhesion and migration of tumor (LM3, 4T1 and MC4-L1) and non-tumor (NMuMG) mouse mammary epithelial cell lines. Tumor cell lines revealed lower cell adhesion (p<0.01) and increased cell migration (p<0.05) after incubation with BA- and WA-CMs vs Control-CMs. In addition, MC4-L1 and LM3 cells significantly increased their migration (p<0.05) in the presence of beige adipocytes. These results suggest that beige adipocytes secrete soluble factors that regulate the behavior of both tumor and non-tumor mouse mammary epithelial cells, favoring tumor progression.