國家衛生研究院 NHRI:Item 3990099045/14112
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    題名: EGFR mutation-harboring lung cancer cells produce CLEC11A with endothelial trophic and tumor-promoting activities
    作者: Lin, TY;Yang, CH;Chou, HC;Cheng, CM;Liu, YW;Wang, JY;Huang, LR;Tsai, SF;Huang, SF;Chen, YR
    貢獻者: Institute of Molecular and Genomic Medicine
    摘要: Simple Summary Tumor angiogenesis is an important step in the progression of solid tumors. Understanding the mechanisms involved in tumor vasculature formation is critical for improving anti-angiogenic strategies. In this study, we reported that EGFR mutation-containing lung cancer cells produced CLEC11A with endothelial trophic and tumor-promoting activities. CLEC11A could be a novel factor involved in tumor angiogenesis. The formation of new blood vessels in solid tumors is regulated by various endothelial trophic factors. We identified that CLEC11A, an extracellular C-type lectin, was over-expressed in lung cancer cell lines harboring mutated EGFR. CLEC11A expression was also frequently elevated in lung adenocarcinoma (LAC) tissues with EGFR mutation. CLEC11A-expressing H1299 cells formed larger tumors in nude mice than did the control cells. The CLEC11A-expressing tumors contained more CD31-positive cells, suggesting that they had a higher angiogenic activity. CLEC11A per se did not induce blood vessel formation, but enhanced angiogenesis triggered by VEGF-A or basic FGF in vivo. Additionally, the expression of small hairpin RNA against CLEC11A (shCLEC11A) in HCC827 LAC cells suppressed their tumorigenic ability. Purified CLEC11A exhibited a chemotactic ability, which is dependent on its integrin-binding RGD and LDT motifs, toward endothelial cells. This chemotactic activity was not affected by the presence of a VEGFR inhibitor. Conditioned medium produced by HCC827-shCLEC11A cells had diminished chemotactic ability toward endothelial cells. CLEC11A treatments increased the levels of active integrin beta 1 that were not associated with activation of focal adhesion kinases in endothelial cells. Our results indicated that CLEC11A was a factor of angiogenic potential and was involved in lung cancer tumorigenesis.
    日期: 2022-03-04
    關聯: Cancers. 2022 Mar 4;14(5):Article number 1356.
    Link to: http://dx.doi.org/10.3390/cancers14051356
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2072-6694&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000767778900001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85125911506
    顯示於類別:[陳怡榮] 期刊論文
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    [蔡世峯] 期刊論文
    [黃麗蓉] 期刊論文

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