{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T05:29:49Z","timestamp":1771997389483,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T00:00:00Z","timestamp":1724284800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100012542","name":"Sichuan Province Science and Technology Support Program","doi-asserted-by":"publisher","award":["2022NSFSC0651"],"award-info":[{"award-number":["2022NSFSC0651"]}],"id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This study aims to investigate the regulatory effects of quercetin extracellular vesicles (EVs)\u2010mediated expression of vascular endothelial growth factor receptor 2 (VEGFR2) in hepatocellular carcinoma (HCC)\u2010derived circulating tumor cells (CTCs) and the underlying mechanisms. CTCs were isolated from patients with pathologically diagnosed HCC, with <jats:italic>VEGFR2<\/jats:italic> expression visualized by fluorescence in situ hybridization (FISH). The human HCC cell line Huh\u20107 and SK\u2010HEP\u20101 were used for in vitro studies to assess EVs uptake, <jats:italic>VEGFR2<\/jats:italic> mRNA transfer, invasion, migration, cancer stem cell (CSC) properties, and VEGF secretion. Results showed that <jats:italic>VEGFR2<\/jats:italic> mRNA was commonly expressed in HCC\u2010CTCs, with a higher incidence in biphenotypic CTCs. Its expression was limited in HCC cell lines, but present in certain liver cells. In vitro experiments confirmed that <jats:italic>VEGFR2<\/jats:italic> mRNA could be transferred to HCC cells via EVs from primary tumor endothelial cells (PTECs), which was impaired by quercetin treatment. Quercetin significantly reduced <jats:italic>VEGFR2<\/jats:italic> mRNA and protein expression in HCC cells, weakened their invasive and metastatic capacities, and diminished VEGFR2\u2010mediated CSC properties. In vivo, quercetin reduced VEGF secretion, impaired angiogenesis, slowed tumor growth, and decreased the number and proportion of VEGFR2\u2010positive CTCs. In summary, <jats:italic>VEGFR2<\/jats:italic> mRNA is present in HCC\u2010CTCs, potentially sourced from PTECs\u2010derived EVs. Quercetin effectively inhibits VEGFR2 expression, impacting HCC cell invasion, metastasis, and CSC characteristics. Besides, it reduces VEGFR2\u2010positive CTCs in vivo. These effects support its therapeutic potential in HCC treatment by targeting the angiogenesis and tumor dissemination pathway.<\/jats:p>","DOI":"10.1002\/mc.23807","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T20:50:52Z","timestamp":1724359852000},"page":"2254-2268","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Quercetin inhibits endothelial &amp; hepatocellular carcinoma cell crosstalk via reducing extracellular vesicle\u2010mediated <i>VEGFR2<\/i> mRNA transfer"],"prefix":"10.1002","volume":"63","author":[{"given":"Wei","family":"Xiong","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Surgery Sichuan Academy of Medical Science &amp; Sichuan Provincial People's Hospital Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of 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