Vessels encapsulating tumor clusters in hepatocellular carcinoma: a distinct metastatic pathway with diagnostic and therapeutic significance

Vessels encapsulating tumor clusters (VETC) represent a distinct vascular pattern that promotes metastasis via a mechanism independent of epithelial-mesenchymal transition (EMT), offering novel perspectives on metastasis research. Defined by sinusoid-like endothelial networks that enclose cohesive tumor cell aggregates, VETC enables collective hematogenous spread while preserving intercellular adhesion. Here, we reviewed the pathophysiological significance of VETC across solid tumors, with particular emphasis on hepatocellular carcinoma (HCC). Epidemiological data reveal that VETC prevalence varies significantly with tumor stage, etiology, and diagnostic criteria, and is strongly associated with aggressive features including microvascular invasion, multinodularity and immune exclusion. Mechanistically, VETC formation is driven by an angiopoietin-2 (Ang2)-centric network, involving crosstalk between the microRNA (miRNA)–androgen receptor (AR) pathway and tumor-associated macrophage-mediated vascular remodeling. Emerging therapeutic strategies, such as Ang2 inhibition combined with immune checkpoint blockade, vascular normalization, and complementary medicine, show promise in preclinical models. Clinically, VETC is an independent prognostic biomarker, offering greater predictive accuracy for recurrence than conventional staging systems. Despite this progress, challenges remain in standardizing diagnostic criteria, resolving spatiotemporal heterogeneity, and translating mechanistic insights into effective combination therapies. VETC defines a new paradigm at the intersection of vascular biology, immune evasion, and collective metastasis, with significant implications for precision oncology.