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María Gómez-Serrano: Extracellular vesicles from tumor-associated adipocytes: characterization of their functional role in the ovarian cancer microenvironment

AIM: Ascites from OC patients contains substantial amounts of EVs originating from both tumor and tumor-associated host cells, such as macrophages or adipocytes. It has been shown that these EVs possess tumor-promoting and immune-suppressive properties. Reprogrammed adipocytes to cancer-associated adipocytes (CAAs) in the omentum have been closely related to OC progression and therapy resistance. Despite the clinical importance of the NF-κB-driven tumor secretome in OC, the contribution of omental adipocytes remains poorly understood. The aim of this project is to unravel molecular signatures of EVs released by tumor-associated adipocytes (Ad-EVs) and the evaluation of their biological function in OC progression and chemoresistance.

STATE of the ART: The omentum is a protective adipose structure in the abdomen consisting of two layers of fatty tissue and constitutes the primary site of OC metastasis. Tissue-resident adipocytes and fibroblasts in the omentum are converted to CAAs and cancer-associated fibroblasts (CAFs) by tumor-derived mediators and are instrumental in creating a TME with strong metastasis-promoting effects. However, how Ad-EVs are integrated into the CAA reprogramming and how they integrate into the inflammatory secretome is still poorly understood. Interestingly, Ad-EV release and composition vary over the adipogenesis process, and pro-inflammatory stimuli like TNF-alpha or hypoxic conditions on adipocytes have been shown to promote leucocyte attachment in endothelial cells through Ad-EVs.