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 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 desmoid formation 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.
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.
|Number of pages||11|
|Journal||European journal of cancer (Oxford, England : 1990)|
|Publication status||Published - 14 Oct 2016|
- Adenomatous Polyposis Coli Protein/genetics
- Colorectal Neoplasms/genetics
- Fibromatosis, Aggressive/genetics
- Gene Knock-In Techniques
- Intestinal Neoplasms/genetics
- Mice, Knockout
- Proto-Oncogene Proteins p21(ras)/genetics
- S100 Calcium-Binding Protein A4/genetics
- Smad4 Protein/genetics