Advances in the mechanisms of extracellular vesicles and circulating tumor cells in hepatocellular carcinoma metastasis (Review).

Metastasis of hepatocellular carcinoma (HCC) is a key factor contributing to poor patient prognosis, with extracellular vesicles (EVs) and circulating tumor cells (CTCs) playing a marked synergistic role in this process. Current research suggests that EVs, acting as essential mediators of intercellular communication, facilitate CTC‑driven HCC recurrence and metastasis by transporting bioactive molecules, including nucleic acids, proteins and lipids. CTCs are regarded as the initiators of tumor metastasis, while the bioactive cargo carried by EVs functions as critical factors that promote their outgrowth. EVs not only remodel the microenvironment of target organs by forming a 'pre‑metastatic niche', but also establish a permissive microenvironment for CTC colonization. This tripartite interplay establishes a cascade model that enhances metastatic dissemination. The present manuscript reviewed the recent advancements and clinical value in understanding the roles of EVs and CTCs in HCC metastasis and recurrence, as well as the mechanisms by which EVs mediate CTC‑driven liver cancer spread, aiming to promote further in‑depth research into HCC metastasis mechanisms.