The Desmoid Tumor Research Foundation

October 2016

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

Author Information

Eugene Lukanidin,Ivana Marolin,Joana Brandao,Katharina Biermann,Mariam Grigorian,Noona Ambartsumian,Paola Collini,Patrick Franken,Riccardo Fodde,Rubina Noori,Yaser Atlasi

Department of Pathology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.,Department of Pathology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: r.fodde@erasmusmc.nl.,Department of Pathology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: Yaser.Atlasi@ncmls.ru.nl.,Department of Pathology, Istituto Nazionale Tumori, Milan, Italy.,Department of Tumor Microenvironment and Metastasis, Danish Cancer Society, Copenhagen Ø, Denmark; Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen N, Denmark.

Publication

Summary

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 Apc1638N/+/KRASV12G 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 desmoidformation where S100a4 deficiency results in a significant reduction of the tumour burden characteristic of the Apc1638N model. In agreement with these results, S100a4 appears to be co-expressed together with mesenchymal stem cell (MSC) markers in desmoid tumours from Apc1638N/+ mice, as well as from sporadic and hereditary human desmoids.

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