Mechanism of Extracellular Vesicle Secretion Associated with TGF-β-Dependent Inflammatory Response in the Tumor Microenvironment
Klaudia Bonowicz, Klaudia Mikołajczyk, Inaz Faisal, Murtaz Qamar, Kerstin Steinbrink, Konrad Kleszczyński, Alina Grzanka, Maciej Gagat
Abstract
Extracellular vesicles (EVs) serve as central mediators in communication between tumor and non-tumor cells. These interactions are largely dependent on the function of the endothelial barrier and the set of receptors present on its surface, as endothelial cells (ECs) are a plenteous source of EVs. The molecular basis for EV secretion and action in the tumor microenvironment (TME) has not been fully elucidated to date. Emerging evidence suggests a prominent role of inflammatory pathways in promoting tumor progression and metastasis. Although transforming growth factor β (TGF-β) is a cytokine with strong immunomodulatory and protective activity in benign and early-stage cancer cells, it plays a pro-tumorigenic role in advanced cancer cells, which is known as the "TGF-β paradox". Thus, the aim of this review is to describe the correlation between EV release, TGF-β-dependent inflammation, and dysregulation of downstream TGF-β signaling in the context of cancer development.