Adipose Tissue-Derived Extracellular Vesicles and the Tumor Microenvironment: Revisiting the Hallmarks of Cancer

Simple Summary Increased body fat is associated with an increased risk of 13 different cancer types. Recent findings have demonstrated a close relationship between extracellular vesicles released by adipose tissues and the establishment and progression of several types of cancers and metastasis. However, detailed information about the establishment of such cooperation is still lacking. We provide evidence to support that extracellular vesicles secreted by adipose tissues may carry tumoral molecules that modulate the behavior and functions of cancer cells, as described in the seminal report "The Hallmarks of Cancer" by Hanahan and Weinberg, published in the early 2000s. Extracellular vesicles (EVs) are crucial elements that sustain the communication between tumor cells and their microenvironment, and have emerged as a widespread mechanism of tumor formation and metastasis. In obesity, the adipose tissue becomes hypertrophic and hyperplastic, triggering increased production of pro-inflammatory adipokines, such as tumor necrosis factor alpha, interleukin 6, interleukin 1, and leptin. Furthermore, obese adipose tissue undergoes dysregulation in the cargo content of the released EVs, resulting in an increased content of pro-inflammatory proteins, fatty acids, and oncogenic microRNAs. These alterations drive obesity-associated inflammatory responses both locally and systemically. After being ignored for a long time, adipose tissues have recently received considerable attention as a major player in tumor microenvironment-linked obesity and cancer. The role of adipose tissue in the establishment and progression of cancer is reinforced by its high plasticity and inflammatory content. Such a relationship may be established by direct contact between adipocytes and cancer cells within the microenvironment or systemically, via EV-mediated cell-to-cell communication. Here, we highlight cues evidencing the influence of adipose tissue-derived EVs on the hallmarks of cancer, which are critical for tumor malignancy.