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Article: Nidogen 1‐Enriched Extracellular Vesicles Facilitate Extrahepatic Metastasis of Liver Cancer by Activating Pulmonary Fibroblasts to Secrete Tumor Necrosis Factor Receptor 1

TitleNidogen 1‐Enriched Extracellular Vesicles Facilitate Extrahepatic Metastasis of Liver Cancer by Activating Pulmonary Fibroblasts to Secrete Tumor Necrosis Factor Receptor 1
Authors
Keywordsextracellular vesicles
hepatocellular carcinoma
nidogen 1
pre‐metastatic niche
tumor necrosis factor receptor 1
Issue Date2020
PublisherWiley Open Access. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2198-3844
Citation
Advanced Science, 2020, v. 7 n. 21, p. article no. 2002157 How to Cite?
AbstractIn hepatocellular carcinoma (HCC) patients with extrahepatic metastasis, the lung is the most frequent site of metastasis. However, how the lung microenvironment favors disseminated cells remains unclear. Here, it is found that nidogen 1 (NID1) in metastatic HCC cell‐derived extracellular vesicles (EVs) promotes pre‐metastatic niche formation in the lung by enhancing angiogenesis and pulmonary endothelial permeability to facilitate colonization of tumor cells and extrahepatic metastasis. EV‐NID1 also activates fibroblasts, which secrete tumor necrosis factor receptor 1 (TNFR1), facilitate lung colonization of tumor cells, and augment HCC cell growth and motility. Administration of anti‐TNFR1 antibody effectively diminishes lung metastasis induced by the metastatic HCC cell‐derived EVs in mice. In the clinical perspective, analysis of serum EV‐NID1 and TNFR1 in HCC patients reveals their positive correlation and association with tumor stages suggesting the potential of these molecules as noninvasive biomarkers for the early detection of HCC. In conclusion, these results demonstrate the interplay of HCC EVs and activated fibroblasts in pre‐metastatic niche formation and how blockage of their functions inhibits distant metastasis to the lungs. This study offers promise for the new direction of HCC treatment by targeting oncogenic EV components and their mediated pathways.
Persistent Identifierhttp://hdl.handle.net/10722/293654
ISSN
2018 Impact Factor: 15.804
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorMao, X-
dc.contributor.authorTey, SK-
dc.contributor.authorYeung, CLS-
dc.contributor.authorKwong, EML-
dc.contributor.authorFung, YME-
dc.contributor.authorChung, CYS-
dc.contributor.authorMak, LY-
dc.contributor.authorWong, DKH-
dc.contributor.authorYuen, MF-
dc.contributor.authorHo, JCM-
dc.contributor.authorPang, H-
dc.contributor.authorWong, MP-
dc.contributor.authorLeung, CON-
dc.contributor.authorLee, TKW-
dc.contributor.authorMa, V-
dc.contributor.authorCho, WCS-
dc.contributor.authorCao, P-
dc.contributor.authorXu, X-
dc.contributor.authorGao, Y-
dc.contributor.authorYam, JWP-
dc.date.accessioned2020-11-23T08:19:54Z-
dc.date.available2020-11-23T08:19:54Z-
dc.date.issued2020-
dc.identifier.citationAdvanced Science, 2020, v. 7 n. 21, p. article no. 2002157-
dc.identifier.issn2198-3844-
dc.identifier.urihttp://hdl.handle.net/10722/293654-
dc.description.abstractIn hepatocellular carcinoma (HCC) patients with extrahepatic metastasis, the lung is the most frequent site of metastasis. However, how the lung microenvironment favors disseminated cells remains unclear. Here, it is found that nidogen 1 (NID1) in metastatic HCC cell‐derived extracellular vesicles (EVs) promotes pre‐metastatic niche formation in the lung by enhancing angiogenesis and pulmonary endothelial permeability to facilitate colonization of tumor cells and extrahepatic metastasis. EV‐NID1 also activates fibroblasts, which secrete tumor necrosis factor receptor 1 (TNFR1), facilitate lung colonization of tumor cells, and augment HCC cell growth and motility. Administration of anti‐TNFR1 antibody effectively diminishes lung metastasis induced by the metastatic HCC cell‐derived EVs in mice. In the clinical perspective, analysis of serum EV‐NID1 and TNFR1 in HCC patients reveals their positive correlation and association with tumor stages suggesting the potential of these molecules as noninvasive biomarkers for the early detection of HCC. In conclusion, these results demonstrate the interplay of HCC EVs and activated fibroblasts in pre‐metastatic niche formation and how blockage of their functions inhibits distant metastasis to the lungs. This study offers promise for the new direction of HCC treatment by targeting oncogenic EV components and their mediated pathways.-
dc.languageeng-
dc.publisherWiley Open Access. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2198-3844-
dc.relation.ispartofAdvanced Science-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectextracellular vesicles-
dc.subjecthepatocellular carcinoma-
dc.subjectnidogen 1-
dc.subjectpre‐metastatic niche-
dc.subjecttumor necrosis factor receptor 1-
dc.titleNidogen 1‐Enriched Extracellular Vesicles Facilitate Extrahepatic Metastasis of Liver Cancer by Activating Pulmonary Fibroblasts to Secrete Tumor Necrosis Factor Receptor 1-
dc.typeArticle-
dc.identifier.emailMao, X: susanmao@hku.hk-
dc.identifier.emailTey, SK: szekeong@hku.hk-
dc.identifier.emailYeung, CLS: u3511157@hku.hk-
dc.identifier.emailFung, YME: eva.fungym@hku.hk-
dc.identifier.emailChung, CYS: cyschung@hku.hk-
dc.identifier.emailMak, LY: lungyi@hku.hk-
dc.identifier.emailWong, DKH: danywong@hku.hk-
dc.identifier.emailYuen, MF: mfyuen@hku.hk-
dc.identifier.emailHo, JCM: jhocm@hku.hk-
dc.identifier.emailPang, H: herbpang@hku.hk-
dc.identifier.emailWong, MP: mwpik@hku.hk-
dc.identifier.emailYam, JWP: judyyam@pathology.hku.hk-
dc.identifier.authorityFung, YME=rp01986-
dc.identifier.authorityChung, CYS=rp02672-
dc.identifier.authorityMak, LY=rp02668-
dc.identifier.authorityWong, DKH=rp00492-
dc.identifier.authorityYuen, MF=rp00479-
dc.identifier.authorityHo, JCM=rp00258-
dc.identifier.authorityPang, H=rp01857-
dc.identifier.authorityWong, MP=rp00348-
dc.identifier.authorityYam, JWP=rp00468-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1002/advs.202002157-
dc.identifier.scopuseid_2-s2.0-85089533361-
dc.identifier.hkuros318992-
dc.identifier.hkuros319884-
dc.identifier.volume7-
dc.identifier.issue21-
dc.identifier.spagearticle no. 2002157-
dc.identifier.epagearticle no. 2002157-
dc.identifier.isiWOS:000560680200001-
dc.publisher.placeGermany-
dc.identifier.issnl2198-3844-

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