Cancer‑associated fibroblast‑derived extracellular vesicles in the tumor microenvironment and their medical importance (Review)

Abstract

Cancer is a heterogeneous group of diseases that can originate in any tissue or organ of the body, which is characterized by the uncontrollable proliferation of abnormal cells and, in some cases, the invasion of nearby tissues or other parts of the body.In recent decades, research has expanded beyond cancer cells, considering the complex interactions within the surrounding tissues due to the heterogeneous nature of cancer.Notably, cancer cells release extracellular vesicles (EVs) into the tumor microenvironment (TME), which influence stromal cells; specifically, they induce the reprogramming of fibroblasts into the cancer-associated fibroblast (CAF) phenotype, making these cells important targets of EV-mediated cross-talk.Accordingly, CAFs serve a key role in tumorigenesis, angiogenesis, tumor development, metastasis and drug resistance by secreting various pro-oncogenic factors.In addition, CAFs can secrete EVs, which further contribute to these processes.These EVs function as a unique form of intercellular communication that can promote cell proliferation and survival, help shape the TME, and increase invasive and metastatic activity.The present review was prompted by the growing recognition of the crucial yet still incompletely understood role of CAF-derived EVs from the TME in driving tumorigenesis, growth and metastasis, highlighting the need for further exploration.