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ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Virus and Host
Volume 14 - 2024 |
doi: 10.3389/fcimb.2024.1415356
This article is part of the Research Topic Extrapulmonary manifestations of SARS-CoV-2 infection and COVID-19 vaccine adverse effects View all 6 articles
Exosomes derived from syncytia induced by SARS-2-S promote the proliferation and metastasis of hepatocellular carcinoma cells
Provisionally accepted
Tinghui Fan
1
Haotian Lin
1
Linfei Huang
1
Huilong Li
1*
Li Zhou
1
Xiaoyu Tian
1*
Ruzhou Zhao
1*
Yanhong Zhang
1*
Xiaopan Yang
1
Luming Wan
1
Hui Zhong
1*
Nan Jiang
2*
Congwen Wei
1*- 1 Beijing Institute of Biotechnology, Beijing, China
- 2 Department of Pharmacy, Chinese PLA General Hospital, Beijing, China
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 molecular mechanism 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 purified from the cell supernatant and verified by nanoparticle tracking analysis (NTA), Western blot (WB) analysis and scanning electron microscopy (SEM). Differentially expressed proteins in syncytia-derived exosomes (Syn-Exos) and their functions was analyzed by Proteomic sequencing. Syn-Exo-mediated promotion of hepatocellular carcinoma cells was measured 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 sequencing revealed that proteins that regulate cell proliferation and metastasis in Syn-Exos were significantly upregulated. Syn-Exos promote the proliferation and migration of hepatocellular carcinoma cells. 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: Syn-Exos induced by SARS-2-S can promote the proliferation and metastasis of hepatocellular carcinoma cells.
Keywords: SARS-2-S, syncytia, Exosomes, Hepatocellular Carcinoma, proliferation, metastasis
Received: 10 Apr 2024; Accepted: 29 Oct 2024.
Copyright: © 2024 Fan, Lin, Huang, Li, Zhou, Tian, Zhao, Zhang, Yang, Wan, Zhong, Jiang and Wei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Huilong Li, Beijing Institute of Biotechnology, Beijing, China
Xiaoyu Tian, Beijing Institute of Biotechnology, Beijing, China
Ruzhou Zhao, Beijing Institute of Biotechnology, Beijing, China
Yanhong Zhang, Beijing Institute of Biotechnology, Beijing, China
Hui Zhong, Beijing Institute of Biotechnology, Beijing, China
Nan Jiang, Department of Pharmacy, Chinese PLA General Hospital, Beijing, China
Congwen Wei, Beijing Institute of Biotechnology, Beijing, China
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