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

Abstract

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 α, 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.

Mediator Complex Subunit 19 Promotes the Development of Hepatocellular Carcinoma by Regulating the AKT/mTOR Signaling Pathway

“…In obesity studies, adipose tissue inflammation is a key process that promotes cancer ( 54 , 55 ). The tumor-promoting effect of obesity alters the level of the microenvironment and inflammatory Mediators and affects the level and function of immune infiltrating cells.…”

Peri-Prostatic Adipocyte-Released TGFβ Enhances Prostate Cancer Cell Motility by Upregulation of Connective Tissue Growth Factor

“…In addition, the ability of adipocyte secretome to promote metastatic expansion has been clearly demonstrated in breast cancer [ 21 ]. There is growing evidence that adipocytes promote the malignant behavior of cancer cells [ 22 ]. Here, we show that AdipoCM from PPAT promotes migration in AI PCa cells through TGF-β upregulation of CTGF ( Figure 6 ).…”

Extracellular Vesicles in Breast Cancer: From Biology and Function to Clinical Diagnosis and Therapeutic Management

“…Adipocyte tissue (AT)-derived SEVs can also enhance growth, motility, and invasion, induce stem cell-like properties, and specific EMT features in estrogen receptor (ER)-positive and TNBC cells [ 202 ]. Among the AT SEVs activated signaling pathways in BC cells are Hippo [ 203 ], HIF-1α [ 202 ], ERK [ 204 ], Wnt/β-catenin [ 205 ], JAK/STAT3 [ 206 ], PI3K/AKT, and TGFbeta/Smad [ 207 ] (For review, [ 208 ]).…”