The role of S100a4 (Mts1) in Apc- and Smad4-driven tumour onset and progression
The role of S100a4 (Mts1) in Apc- and Smad4-driven tumour onset and progression
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DOI：
10.1016/j.ejca.2016.09.012
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发表时间：
2016-11-01
影响因子：
8.4
通讯作者：
Fodde, Riccardo
中科院分区：
文献类型：
--
作者：
Atlasi, Yaser;Noori, Rubina;Fodde, Riccardo
简介：S100 a4是一种钙结合蛋白，属于S100蛋白家族，在不同的基质细胞类型中高度表达。S100 A4已被报道为与肿瘤进展和转移相关的结直肠癌预后标志物。方法：在这项研究中，我们使用不同的转基因和敲除小鼠模型分析了S100 a4在肠道肿瘤发生和进展中的体内作用。我们发现Apc和Smad 4突变小鼠中S100 a4的基因消融或过表达不影响肠道肿瘤的发生。相反，Apc（1638 N/+）/KRAS（V12 G）小鼠中S100 a4上皮过表达增加了肠道肿瘤细胞向肝脏的播散，这与其在肿瘤转移中的作用一致。此外，我们报告了S100 a4在硬纤维瘤形成中的新作用，其中S100 a4缺乏导致Apc（1638 N）模型的肿瘤负荷特征显著降低。与这些结果相一致，S100 a4似乎是共同表达与间充质干细胞（MSC）标志物在硬纤维瘤从Apc（1638 N/+）小鼠，以及从散发性和遗传性的人类desmoids.Conclusion：我们的数据提供了第一份报告在体内的作用S100 a4在肠道肿瘤的发生和描述了一个新的作用S100 a4在硬纤维瘤形成的病因。(C)2016爱思唯尔有限公司版权所有
Introduction: S100a4 is a calcium-binding protein belonging to the family of S100-proteins, highly expressed in different stromal cell types. S100A4 has been reported as a prognostic marker in colorectal cancer in association with tumour progression and metastasis.Methods: In this study, we analysed the in vivo role of S100a4 in intestinal tumour initiation and progression using different transgenic and knockout mouse models.Results: We found that genetic ablation or overexpression of S100a4 in both Apc- and Smad4-mutant mice do not affect tumour initiation in the intestinal tract. In contrast, S100a4 epithelial overexpression in Apc(1638N/+)/KRAS(V12G) mice increases the dissemination of intestinal tumour cells to the liver, in agreement with its role in tumour metastasis. Moreover, we report a novel role for S100a4 in desmoid formation where S100a4 deficiency results in a significant reduction of the tumour burden characteristic of the Apc(1638N) model. In agreement with these results, S100a4 appears to be co-expressed together with mesenchymal stem cell (MSC) markers in desmoid tumours from Apc(1638N/+) mice, as well as from sporadic and hereditary human desmoids.Conclusion: Our data provide the first report on the in vivo role of S100a4 in intestinal tumourigenesis and describe a new role for S100a4 in the aetiology of desmoids formation. (C) 2016 Elsevier Ltd. All rights reserved.