Exosomes derived from syncytia induced by SARS-2-S promote the proliferation and metastasis of hepatocellular carcinoma cells

ABSTRACT: Introduction: Coronavirus disease 2019 (COVID-19) is characterized by fever, fatigue, dry cough, dyspnea, mild pneumonia and acute lung injury (ALI), which can lead to acute respiratory distress syndrome (ARDS), and SARS-CoV-2 can accelerate tumor progression. However, the reason for the increased mortality in cancer patients infected with COVID-19 is unclear. Methods: Colony formation and wound healing assays were performed on Huh-7 cells cocultured with syncytia. Exosomes were extracted from the cell supernatant and verified by nanoparticle tracking analysis (NTA), Western blot (WB) analysis and scanning electron microscopy (SEM). Proteomic sequencing was used to analyze differentially expressed proteins in syncytia-derived exosomes (Syn-Exos) and their functions. Syn-Exo-mediated promotion of hepatocellular carcinoma cells was verified by CCK-8 and Transwell migration assays. The mechanism by which Syn-Exos promote tumor growth was analyzed by Western blotting. A patient-derived xenotransplantation (PDX) mouse model was constructed to evaluate the pathological role of the SARS-CoV-2 spike protein (SARS-2-S). The number of syncytia in the tumor tissue sections was determined by immunofluorescence analysis. Results: Syncytium formation promoted the proliferation and migration of hepatocellular carcinoma cells. Proteomic analysis revealed that proteins that regulate cell proliferation and metastasis in Syn-Exos were significantly upregulated. Syn-Exos promoted hepatocellular carcinoma cell proliferation and migration through the JAK1/STAT3 pathway. Animal experiments showed that a pseudotyped lentivirus bearing SARS-2-S (SARS-2-Spp) promoted tumor development in PDX mice. More syncytia were found in tumor tissue from SARS-2-Spp mice than from VSV-Gpp mice. Conclusions: We identified a new mechanism by which patients with COVID-19 develop liver cancer. Syn-Exos induced by SARS-2-S can promote the proliferation and metastasis of hepatocellular carcinoma cells

ORGANISM(S): Mus Musculus

SUBMITTER: Congwen Wei  

PROVIDER: PXD051349 | iProX | Wed Apr 10 00:00:00 BST 2024

REPOSITORIES: iProX