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首页> 外文期刊>Hepatology: Official Journal of the American Association for the Study of Liver Diseases >Nuclear Expression of S100A4 Calcium-Binding Protein Increases Cholangiocarcinoma Invasiveness and Metastasization
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Nuclear Expression of S100A4 Calcium-Binding Protein Increases Cholangiocarcinoma Invasiveness and Metastasization

机译：S100A4钙结合蛋白的核表达增加胆管癌的侵袭和转移。

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Cholangiocarcinoma (CCA) carries a severe prognosis because of its strong invasiveness and early metastasization. In several patients, otherwise eligible for surgical resection, micrometastasis are already present at the time of surgery. The mechanisms responsible for CCA invasiveness are unclear. S100A4, a member of the S100 family of small Ca -binding proteins, is expressed in mesenchymal cells, regulates cell motility in several cell types, and is expressed in some epithelial cancers. Thus, we aimed to study the role of S100A4 in CCA invasiveness and metastasization. The expression of S100A4 was studied by immuno-histochemistry in 93 human liver samples of CCA patients undergoing surgical resection and correlated with metastases development (67 cases) and patient survival following surgery using log rank tests and multivariate analysis. S100A4 expression was studied in EGI-1 and TFK-1, human CCA cell lines with and without nuclear S100A4 expression, respectively. Metastatic properties of CCA cells were assessed by xenotransplantation in severe combined immunodeficiency (SCID) mice after transduction with lentiviral vectors encoding firefly luciferase gene. Proliferation, motility (wound healing), invasiveness (Boyden chamber), and metalloproteinases (MMPs) secretion were studied in CCA cells, with or without lentiviral silencing of S100A4. Nuclear expression of S100A4 by neoplas-tic ducts was a strong predictor of metastasization and reduced survival after resection (P < 0.01). EGI-1 CCA cells showed stronger metastatic properties than TFK-1 when xenotransplanted in SCID mice. S100A4-silenced EGI-1 cells showed significantly reduced motility, invasiveness, and MMP-9 secretion in vitro, without changes in cell proliferation. Conclusion: Nuclear S100A4 identifies a subset of CCA patients with a poor prognosis after surgical resection. Nuclear expression of S100A4 increases CCA cells invasiveness and metastasization, indicating that S100A4 may also represent a po...
机译：胆管癌（CCA）由于其强大的浸润性和早期转移性而预后严重。在其他一些符合手术切除条件的患者中，手术时已经存在微转移。造成CCA侵袭的机制尚不清楚。 S100A4是小Ca结合蛋白S100家族的成员，在间充质细胞中表达，调节几种细胞类型的细胞运动，并在某些上皮癌中表达。因此，我们旨在研究S100A4在CCA侵袭和转移中的作用。通过免疫组织化学方法在93例接受手术切除的CCA患者的人肝样本中研究了S100A4的表达，并通过对数秩检验和多变量分析与转移灶（67例）和术后患者生存率相关。在具有或不具有核S100A4表达的人CCA细胞系EGI-1和TFK-1中研究了S100A4表达。在编码萤火虫荧光素酶基因的慢病毒载体转导后，通过异种移植在严重的联合免疫缺陷（SCID）小鼠中评估CCA细胞的转移特性。在有或没有慢病毒沉默的S100A4中，研究了CCA细胞的增殖，运动性（伤口愈合），侵袭性（博伊登室）和金属蛋白酶（MMP）分泌。赘生性导管对S100A4的核表达是转移的一个强有力的预测指标，并且切除后的生存率降低（P <0.01）。当在SCID小鼠中异种移植时，EGI-1 CCA细胞显示出比TFK-1更强的转移特性。 S100A4沉默的EGI-1细胞在体外显示出明显降低的运动性，侵袭性和MMP-9分泌，而细胞增殖没有变化。结论：S100A4核素可识别出一部分CCA患者，这些患者在手术切除后预后较差。 S100A4的核表达增加了CCA细胞的侵袭性和转移能力，表明S100A4可能还代表着一种...

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