title: The role of S100a4 (Mts1) in Apc- and Smad4-driven tumour onset and progression.
abstract: 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.
  
  
  
  In this study, we analysed the in vivo role of S100a4 in intestinal tumour initiation and progression using different transgenic and knockout mouse models.
  
  
  
  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/+/KRASV12Gmice 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 Apc1638Nmodel. 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.
  
  
  
  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.
authors.affiliation: Department of Pathology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: Yaser.Atlasi@ncmls.ru.nl.
authors.forename: Yaser
authors.initials: Y
authors.lastname: Atlasi
authors.affiliation: Department of Pathology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Rubina
authors.initials: R
authors.lastname: Noori
authors.affiliation: Department of Pathology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Ivana
authors.initials: I
authors.lastname: Marolin
authors.affiliation: Department of Pathology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Patrick
authors.initials: P
authors.lastname: Franken
authors.affiliation: Department of Pathology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Joana
authors.initials: J
authors.lastname: Brandao
authors.affiliation: Department of Pathology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Katharina
authors.initials: K
authors.lastname: Biermann
authors.affiliation: Department of Pathology, Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Collini
authors.affiliation: 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.
authors.forename: Mariam
authors.initials: M
authors.lastname: Grigorian
authors.affiliation: 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.
authors.forename: Eugene
authors.initials: E
authors.lastname: Lukanidin
authors.affiliation: 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.
authors.forename: Noona
authors.initials: N
authors.lastname: Ambartsumian
authors.affiliation: Department of Pathology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: r.fodde@erasmusmc.nl.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Fodde
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D018222:Desmoid Tumors / Q000235:genetics*; D055879:Gene Knock-In Techniques; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D000071999:S100 Calcium-Binding Protein A4 / Q000235:genetics* / Q000378:metabolism; D051901:Smad4 Protein / Q000235:genetics
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D000071999:S100 Calcium-Binding Protein A4; C470944:S100a4 protein, mouse; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; C000613192:adenomatous polyposis coli protein, mouse; C077591:S100A4 protein, human; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Apc; Colorectal cancer; Desmoids; Mts1; S100a4; Smad4