國家衛生研究院 NHRI:Item 3990099045/9741
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    題名: Paracrine regulation of matrix metalloproteinases contributes to cancer cell invasion by hepatocellular carcinoma-secreted 14-3-3sigma
    作者: Liu, CC;Chang, TC;Lin, YT;Yu, YL;Ko, BS;Sung, LY;Liou, JY
    貢獻者: Institute of Cellular and Systems Medicine
    摘要: 14-3-3sigma overexpression results in enhanced hepatocellular carcinoma (HCC) cell migration and HCC tumor vascular-invasion is significantly associated with 14-3-3sigma expression. However, increased expression of 14-3-3sigma paradoxically suppresses in vitro cell invasion of HCC. We hypothesize that surrounding tumor-associated stromal cells play a crucial role in 14-3-3sigma-regulated HCC cell invasion. In this study, H68 fibroblasts, THP-1 and phorbol-12-myristate-13-acetate (PMA)-treated THP-1 (PMA-THP-1) cells were incubated with conditioned media of control (control-CM) and 14-3-3sigma-overepxressing cells (14-3-3sigma-CM), followed by co-culture with HCC cells. Invasiveness of HCC cells was examined by a Boyden chamber assay. HCC cells co-cultured with 14-3-3sigma-CM treated cells significantly enhanced their invasive ability compared with control-CM treated cells. Moreover, incubation with 14-3-3sigma-CM induced differential expression profiles of matrix metalloproteinases (MMPs) in fibroblasts (MMP-1, MMP-2, MMP-9, MMP-12 and MMP-14), THP-1 (MMP-1 and MMP-12) and PMA-THP-1 cells (MMP-2, MMP-12 and MMP-14). In contrast, silencing of 14-3-3sigma by siRNA significantly abolished 14-3-3sigma-CM induced MMPs. In addition, treatment with recombinant 14-3-3sigma (r14-3-3sigma) protein exhibits a similar expression profile of MMPs induced by 14-3-3sigma-CM in fibroblasts, THP-1 and PMA-THP-1 cells. Finally, knockdown of aminopeptidase N (APN) significantly abrogated r14-3-3sigma induced expression of MMPs in HS68 fibroblasts. These results suggest that HCC-secreted 14-3-3sigma promotes expression of MMPs in cancerous surrounding cells via an APN dependent mechanism. 14-3-3sigma has a paracrine effect in educating stromal cells in tumor-associated microenvironment.
    日期: 2016-06
    關聯: Oncotarget. 2016 Jun;7(24):36988-36999.
    Link to: http://dx.doi.org/10.18632/oncotarget.9234
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000377756800115
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84978087042
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