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Article: Clathrin light chain A-enriched small extracellular vesicles remodel microvascular niche to induce hepatocellular carcinoma metastasis

TitleClathrin light chain A-enriched small extracellular vesicles remodel microvascular niche to induce hepatocellular carcinoma metastasis
Authors
Keywordsclathrin light chain A
hepatocellular carcinoma
intercellular communication
premetastatic niche
small extracellular vesicles
vascular permeability
Issue Date1-Aug-2023
PublisherWiley Open Access
Citation
Journal of Extracellular Vesicles, 2023, v. 12, n. 8 How to Cite?
AbstractSmall extracellular vesicles (sEVs) play a key role in exchanging cargoes between cells in tumour microenvironment. This study aimed to elucidate the functions and mechanisms of hepatocellular carcinoma (HCC) derived sEV-clathrin light chain A (CLTA) in remodelling microvascular niche. CLTA level in the circulating sEVs of HCC patients was analysed by enzyme-linked immunosorbent assay (ELISA). The functions of sEV-CLTA in affecting HCC cancerous properties were examined by multiple functional assays. Mass spectrometry was used to identify downstream effectors of sEV-CLTA in human umbilical vein endothelial cells (HUVECs). Tube formation, sprouting, trans-endothelial invasion and vascular leakiness assays were performed to determine the functions of sEV-CLTA and its effector, basigin (BSG) in HUVECs. BSG inhibitor, SP-8356, was tested in a mouse model of patient-derived xenografts (PDXs). Circulating sEVs of HCC patients had markedly enhanced CLTA levels than control individuals and were reduced in patients after surgery. HCC derived sEV-CLTA enhanced HCC cancerous properties, disrupted endothelial integrity and induced angiogenesis. Mechanistically, CLTA remodels microvascular niche by stabilizing and upregulating BSG. Last, SP-8356 alone or in combination with sorafenib attenuated PDXs growth. The study reveals the role of HCC derived sEV-CLTA in microvascular niche formation. Inhibition of CLTA and its mediated pathway may illuminate a new therapeutic strategy for HCC patients.
Persistent Identifierhttp://hdl.handle.net/10722/331590
ISSN
2023 Impact Factor: 15.5
2023 SCImago Journal Rankings: 4.268
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorXu, Y-
dc.contributor.authorYao, Y-
dc.contributor.authorYu, L-
dc.contributor.authorZhang, XX-
dc.contributor.authorMao, XW-
dc.contributor.authorTey, SK-
dc.contributor.authorWong, SWK-
dc.contributor.authorYeung, CLS-
dc.contributor.authorNg, TH-
dc.contributor.authorWong, MY-
dc.contributor.authorChe, CM-
dc.contributor.authorLee, TKW-
dc.contributor.authorGao, Y-
dc.contributor.authorCui, YF-
dc.contributor.authorYam, JWP-
dc.date.accessioned2023-09-21T06:57:11Z-
dc.date.available2023-09-21T06:57:11Z-
dc.date.issued2023-08-01-
dc.identifier.citationJournal of Extracellular Vesicles, 2023, v. 12, n. 8-
dc.identifier.issn2001-3078-
dc.identifier.urihttp://hdl.handle.net/10722/331590-
dc.description.abstractSmall extracellular vesicles (sEVs) play a key role in exchanging cargoes between cells in tumour microenvironment. This study aimed to elucidate the functions and mechanisms of hepatocellular carcinoma (HCC) derived sEV-clathrin light chain A (CLTA) in remodelling microvascular niche. CLTA level in the circulating sEVs of HCC patients was analysed by enzyme-linked immunosorbent assay (ELISA). The functions of sEV-CLTA in affecting HCC cancerous properties were examined by multiple functional assays. Mass spectrometry was used to identify downstream effectors of sEV-CLTA in human umbilical vein endothelial cells (HUVECs). Tube formation, sprouting, trans-endothelial invasion and vascular leakiness assays were performed to determine the functions of sEV-CLTA and its effector, basigin (BSG) in HUVECs. BSG inhibitor, SP-8356, was tested in a mouse model of patient-derived xenografts (PDXs). Circulating sEVs of HCC patients had markedly enhanced CLTA levels than control individuals and were reduced in patients after surgery. HCC derived sEV-CLTA enhanced HCC cancerous properties, disrupted endothelial integrity and induced angiogenesis. Mechanistically, CLTA remodels microvascular niche by stabilizing and upregulating BSG. Last, SP-8356 alone or in combination with sorafenib attenuated PDXs growth. The study reveals the role of HCC derived sEV-CLTA in microvascular niche formation. Inhibition of CLTA and its mediated pathway may illuminate a new therapeutic strategy for HCC patients.-
dc.languageeng-
dc.publisherWiley Open Access-
dc.relation.ispartofJournal of Extracellular Vesicles-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectclathrin light chain A-
dc.subjecthepatocellular carcinoma-
dc.subjectintercellular communication-
dc.subjectpremetastatic niche-
dc.subjectsmall extracellular vesicles-
dc.subjectvascular permeability-
dc.titleClathrin light chain A-enriched small extracellular vesicles remodel microvascular niche to induce hepatocellular carcinoma metastasis-
dc.typeArticle-
dc.identifier.doi10.1002/jev2.12359-
dc.identifier.scopuseid_2-s2.0-85168517559-
dc.identifier.volume12-
dc.identifier.issue8-
dc.identifier.eissn2001-3078-
dc.identifier.isiWOS:001052975800002-
dc.publisher.placeHOBOKEN-
dc.identifier.issnl2001-3078-

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