The role of S100a4 (Mts1) in Apc- and Smad4-driven tumour onset and progression

被引:12
作者
Atlasi, Yaser [1 ,5 ]
Noori, Rubina [1 ]
Marolin, Ivana [1 ]
Franken, Patrick [1 ]
Brandao, Joana [1 ]
Biermann, Katharina [1 ]
Collini, Paola [2 ]
Grigorian, Mariam [3 ,4 ]
Lukanidin, Eugene [3 ,4 ]
Ambartsumian, Noona [3 ,4 ]
Fodde, Riccardo [1 ]
机构
[1] Erasmus Univ, Med Ctr, Erasmus MC Canc Inst, Dept Pathol, Rotterdam, Netherlands
[2] Ist Nazl Tumori, Dept Pathol, Milan, Italy
[3] Danish Canc Soc, Dept Tumor Microenvironm & Metastasis, Copenhagen O, Denmark
[4] Univ Copenhagen, Fac Hlth Sci, Dept Neurosci & Pharmacol, Copenhagen N, Denmark
[5] Radboud Univ Nijmegen, Dept Mol Biol, RIMLS, Nijmegen, Netherlands
关键词
S100a4; Colorectal cancer; Desmoids; Mts1; Apc; Smad4; FAMILIAL ADENOMATOUS POLYPOSIS; BINDING PROTEIN S100A4; MARROW-DERIVED CELLS; COLORECTAL-CANCER; DESMOID TUMORS; AGGRESSIVE FIBROMATOSIS; PROGNOSTIC-SIGNIFICANCE; MESENCHYMAL PROGENITOR; INTESTINAL TUMORS; ENDOTHELIAL-CELLS;
D O I
10.1016/j.ejca.2016.09.012
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:114 / 124
页数:11
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