A research team led by Professor Judy Yam Wai-ping from the Department of Pathology, School of Clinical Medicine, LKS Faculty of Medicine, the University of Hong Kong (HKUMed) has made a significant breakthrough in unveiling an unrecognized signaling pathway mediated by circulating small extracellular vesicles (sEVs) derived from liver cancer patients that promotes liver cancer metastasis. This discovery presents a potential therapeutic strategy for treating liver cancer. The findings have been published in Advanced Science.
Circulating sEVs from HCC patients promote angiogenesis in vitro and in vivo. A) Tube formation assay of HUVECs pretreated with PBS, circulating sEVs of control individuals , and HCC patients at the early stage and late stage . B) HUVECs pretreated with the indicated sEVs were subjected to an endothelial sprouting assay. C) Schematic diagram of the in vivo Matrigel assay. PLC/PRF/5 cells were subcutaneously co-injected with PBS, normal, E-HCC, or L-HCC-sEVs .
is largely driven by the modulation of tumor-derived small extracellular vesicles within the tumor microenvironment.to enter the bloodstream, facilitating their dissemination to distant loci and thus cancer metastasis. Growing evidence suggests that tumor-derived sEVs play a role in modulating angiogenic signaling. Understanding the mechanisms by which sEVs regulate angiogenesis in liver cancer could lead to the development of new therapeutic strategies.
Proteomic profiling of circulating sEVs of control subjects and Hepatocellular Carcinoma individuals revealed von Willibrand factor to be upregulated progressively along the developmental stages of liver cancer. The drastic elevation of sEV-vWF level in HCC patients indicated its potentiality as a non-invasive diagnostic marker for liver cancer.
vWF-enriched sEVs derived from liver cancer cells displayed a significant promoting effect on angiogenesis, tumor-endothelial adhesion and vascular permeability. The
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