國家衛生研究院 NHRI:Item 3990099045/11556
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    题名: Laminin gamma2-enriched extracellular vesicles of oral squamous cell carcinoma cells enhance in vitro lymphangiogenesis via intergrin alpha3-dependent uptake by lymphatic endothelial cells
    其它题名: Laminin γ2-enriched extracellular vesicles of oral squamous cell carcinoma cells enhance in vitro lymphangiogenesis via intergrin α3-dependent uptake by lymphatic endothelial cells
    作者: Wang, SH;Liou, GG;Liu, SH;Chang, JS;Hsiao, JR;Yen, YC;Chen, YL;Wu, WL;Chang, JY;Chen, YW
    贡献者: National Institute of Cancer Research
    摘要: Oral squamous cell carcinoma (OSCC) LN1-l cells previously showed greater capacities for lymphangiogenesis and lymph node metastasis compared to their parental OEC-M1 cells, in addition to an ability to enhance the migration and tube formation of lymphatic endothelial cells (LECs). Purified by a series of differential centrifugations and characterized using electron microscopy, dynamic light scattering, and western blot, LN1-1 cell-derived extracellular vesicles (LN1-1 EVs) were shown to promote LEC migration, tube formation, and uptake by LECs more effectively than did OEC-M1 cell-derived EVs (OEC-M1 EVs). Using stable isotope labeling with amino acids in cell culture/liquid chromatography-tandem mass spectrometry based proteomic platform, the laminin-332 proteins, including laminin alpha3, beta3, and gamma2, were validated as highly expressed proteins in LN1-1 EVs. Clinically, a higher level of laminin-332 was detected in plasma EVs from OSCC patients with lymph node metastasis than in both healthy controls and OSCC patients without lymphatic metastasis, suggesting EV-borne laminin-332 as a novel and non-invasive biomarker for the detection of lymph node metastasis in OSCC. The knockdown of laminin gamma2 and inhibition by anti-laminin-332 neutralizing antibodies impaired LN1-1 EV-mediated LEC migration, tube formation, and uptake by LECs. Importantly, laminin gamma2-deficient EVs showed a reduced ability to drain into lymph nodes in comparison with the control EVs. Additionally, the laminin 332/gamma2-mediated EV uptake was dependent on integrin alpha3 but not beta1, beta4 or alpha6. Collectively, the uptake of laminin gamma2-enriched EVs by LECs enhanced in vitro lymphangiogenesis and EV-borne laminin-332 is thus a viable biomarker for OSCC. This article is protected by copyright. All rights reserved.
    日期: 2019-06-01
    關聯: International Journal of Cancer. 2019 Jun 1;144(11):2795-2810.
    Link to: http://dx.doi.org/10.1002/ijc.32027
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0020-7136&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000467099500017
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85059918171
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