IS WHITE ADIPOCYTES BROWNING INDUCED BY BREAST CANCER CELLS?

GANTOV M; FLETCHER SJ; PISTONE CREYDT V; DRESZMAN R; CROSBIE ML; SANTISO N; URSINO A; AMATO AR; GUTIERREZ L; SACCA PA; CALVO JC; TONEATTO J

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clìnica; 2018

Sociedad Argentina de Investigación Clínica (SAIC)

Stromal-epithelial interactions mediate the development and progression ofbreast cancer. Adipocytes are the predominant stromal cell type in breast tissue. We showed that explants from human breast cancer adipose tissue (hATT) secrete a different set of factors compared to that from normal tissue explants (hATN), which may induce browning of white adipocytes. However, adipocyte characteristics involved in this process remain poorly understood. Here, weevaluated the effects of conditioned media (CMs) of hATN and hATT on expressionand localization of different brown and white fat-specific markers on 3T3-L1adipocytes by indirect immunofluorescence. Interestingly, adipocytes exposed tohATT CMs displayed characteristics that morphologically resembled brown adipocytes. These brown-like adipocytes showed increased UCP1 and Glut4, andnumber of micro-lipid droplets (LDs, stained for perilipin). Contrarily,adipocytes exposed to hATN CMs increased LDs size, characteristic of white adipocytes. Importantly, immunostaining showed that perilipin was homogeneously distributed on the surface of large-LDs, while a lower intensity signal for UCP1 and Glut4 was observed. Therefore, these findings led us to hypothesize that the changes observed in hATT attached to the tumor could result from a browning process of white adipocytes influenced by the adjacent cancer cells.To demonstrate this, we used indirect co-culture of 3T3-L1 adipocytes and various breast cancer cells. Surprisingly, transwell co-culture with NMuMG orLM3 decreased UCP1 expression (p