Mitochondria response to obesity-related inflammation in a breast cancer 3D culture approach

Abstract

[eng] Mitochondria are closely connected to breast cancer and its progression. Obesity influences breast cancer cells by the production of hormones and proinflammatory cytokines. Here, we analyzed gene expression of different biomarkers associated to mitochondria response, epithelial-mesenchymal transition and stemness and evaluated estrogen receptor ratio (ERα/ERß) in human breast cancer cell lines (T47D, MCF7 and MDA-MB-231), with a great variety in this ratio, after ELIT (17β-estradiol, leptin, IL-6 and TNFα) treatment. This treatment mimics the hormonal situation and the obesity-related inflammation state of a postmenopausal obese woman. Furthermore, breast cancer stem cells(BCSCs), which have a role in stemness, tumor growth and metastasis, can be studied in detail using 3D cultures. To analyze the effect of ELIT in BCSCs subpopulations, mammospheres cultures were performed. We observed that in T47D cells mitochondria response to ELIT was to enhance autophagy which could be as a quality control to promote stemness and self-renewal, that was stimulated in this cell line, as well as an increase in the ERα/ERß ratio. An insufficient or absent mitochondria response was linked to an activation of the epithelial-mesenchymal transition mechanisms in MCF7 cell line, which also suffered a reduction in ERα/ERß ratio, and in MDA-MB-231 cells, while were not induced in T47D cell line. Moreover, ELIT increased mammosphere forming efficiency (MFE) in T47D and MCF7 cell lines, especially in T47D cells. Thus, our results propose a relationship between mitochondrial state and migration or stemness activity in breast cancer cell lines with differences in the expression of the estrogen receptor subtypes, especially ERα and ERß, in an obesity-related inflammation condition.