Fig. 6.

Schematic representation of the role of tumor-surrounding adipocytes in breast cancer resistance to doxorubicin (DOX). DOX enters tumor cells by passive diffusion and accumulates in the nucleus. Upon stimulation with adipocyte soluble factors, the level of major vault protein (MVP) increases, promoting DOX nuclear efflux. This efflux is followed by sequestration of DOX in cytoplasmic vesicles, and extracellular efflux of the drug is mediated through secretion of these vesicles (extracellular vesicles, EV). This adipocyte-mediated mechanism contributes to the occurrence of a resistant phenotype that is amplified by obesity