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

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

doi:10.1016/j.ejca.2016.09.012

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

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

School of Medicine, Dentistry and Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	114-124
Number of pages	11
Journal	European Journal of Cancer (Oxford, England : 1990)
Volume	68
DOIs	https://doi.org/10.1016/j.ejca.2016.09.012
Publication status	Published - 14 Oct 2016

Keywords

Adenomatous Polyposis Coli Protein/genetics
Animals
Carcinogenesis/genetics
Colorectal Neoplasms/genetics
Fibromatosis, Aggressive/genetics
Gene Knock-In Techniques
Humans
Intestinal Neoplasms/genetics
Mice
Mice, Knockout
Mutation
Proto-Oncogene Proteins p21(ras)/genetics
S100 Calcium-Binding Protein A4/genetics
Smad4 Protein/genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ejca.2016.09.012Licence: Unspecified

Yaser Atlasi
- Y.Atlasiqub.acuk
- School of Medicine, Dentistry and Biomedical Sciences - Senior Lecturer
- Patrick G Johnston Centre for Cancer Research
Person: Academic

Cite this

@article{16df308e5c8c40f1ba5a07f8542f67dd,

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

abstract = "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.",

keywords = "Adenomatous Polyposis Coli Protein/genetics, Animals, Carcinogenesis/genetics, Colorectal Neoplasms/genetics, Fibromatosis, Aggressive/genetics, Gene Knock-In Techniques, Humans, Intestinal Neoplasms/genetics, Mice, Mice, Knockout, Mutation, Proto-Oncogene Proteins p21(ras)/genetics, S100 Calcium-Binding Protein A4/genetics, Smad4 Protein/genetics",

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

year = "2016",

month = oct,

day = "14",

doi = "10.1016/j.ejca.2016.09.012",

language = "English",

volume = "68",

pages = "114--124",

journal = "European Journal of Cancer (Oxford, England : 1990)",

issn = "0959-8049",

publisher = "Elsevier Ltd",

}

TY - JOUR

T1 - The role of S100a4 (Mts1) in Apc- and Smad4-driven tumour onset and progression

AU - Atlasi, Yaser

AU - Noori, Rubina

AU - Marolin, Ivana

AU - Franken, Patrick

AU - Brandao, Joana

AU - Biermann, Katharina

AU - Collini, Paola

AU - Grigorian, Mariam

AU - Lukanidin, Eugene

AU - Ambartsumian, Noona

AU - Fodde, Riccardo

PY - 2016/10/14

Y1 - 2016/10/14

N2 - 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.

AB - 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.

KW - Adenomatous Polyposis Coli Protein/genetics

KW - Animals

KW - Carcinogenesis/genetics

KW - Colorectal Neoplasms/genetics

KW - Fibromatosis, Aggressive/genetics

KW - Gene Knock-In Techniques

KW - Humans

KW - Intestinal Neoplasms/genetics

KW - Mice

KW - Mice, Knockout

KW - Mutation

KW - Proto-Oncogene Proteins p21(ras)/genetics

KW - S100 Calcium-Binding Protein A4/genetics

KW - Smad4 Protein/genetics

U2 - 10.1016/j.ejca.2016.09.012

DO - 10.1016/j.ejca.2016.09.012

M3 - Article

C2 - 27750112

SN - 0959-8049

VL - 68

SP - 114

EP - 124

JO - European Journal of Cancer (Oxford, England : 1990)

JF - European Journal of Cancer (Oxford, England : 1990)

ER -

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

Abstract

Keywords

UN SDGs

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Yaser Atlasi

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