A research team at the Department of Pathology, LKS Facultyof Medicine, The University of Hong Kong (HKUMed) in collaboration with HongKong and mainland researchers, has revealed an unrecognized function of patient-derived circulating extracellular vesicles (EVs) in liver cancer metastasis. These ground-breaking findings, giving insights into early diagnosis and a new therapeutic strategy for liver cancer, are now published in Journal of Hepatology.
Using proteomic profiling to compare circulating EVsobtained from the sera of control individuals and liver cancer patients atearly and advanced stages, the team discovered a stepwise upregulation of polymeric immunoglobulin receptor (pIgR) in the circulating EVs from control individuals, cancer patients at the early stage to those at the advanced stage.
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The level of EV-pIgR decreases in about 70% of patients after surgery. These findings suggest the crucial role of EV-pIgR in liver cancer development and its potentiality as a non-invasive diagnostic marker for liver cancer.
The research team further demonstrated the functions ofpIgR-enriched EVs, obtained from serum of cancer patients and metastatic livercancer cell lines, in promoting cancer stemness, tumorigenesis and metastasis in a mouse model of liver cancer.
The oncogenic effect of EVs is dramatically compromised when the expression or function of pIgR is suppressed. The team also unraveled the molecular mechanism by which EV-pIgR activates PDK1/Akt/GSK3β/β-catenin signaling axis in cancer cells.
Sorafenib is the first-line systemic treatment for advancedinoperable liver cancer. The team showed that combined treatment usinganti-pIgR antibody and sorafenib is more effective than sorafenib alone in inhibiting tumor development in a patient-derived xenograft mouse model.
The outcome suggests an alternative effective therapeutic approach for cancer patients.
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