Cell Reports (Oct 2013)
Tenascin-C Downregulates Wnt Inhibitor Dickkopf-1, Promoting Tumorigenesis in a Neuroendocrine Tumor Model
- Falk Saupe,
- Anja Schwenzer,
- Yundan Jia,
- Isabelle Gasser,
- Caroline Spenlé,
- Benoit Langlois,
- Martial Kammerer,
- Olivier Lefebvre,
- Ruslan Hlushchuk,
- Tristan Rupp,
- Marija Marko,
- Michael van der Heyden,
- Gérard Cremel,
- Christiane Arnold,
- Annick Klein,
- Patricia Simon-Assmann,
- Valentin Djonov,
- Agnès Neuville-Méchine,
- Irene Esposito,
- Julia Slotta-Huspenina,
- Klaus-Peter Janssen,
- Olivier de Wever,
- Gerhard Christofori,
- Thomas Hussenet,
- Gertraud Orend
Affiliations
- Falk Saupe
- Inserm U1109, MN3T Team, The Microenvironmental Niche in Tumorigenesis and Targeted Therapy, 3 Avenue Molière, 67200 Strasbourg, France
- Anja Schwenzer
- Inserm U1109, MN3T Team, The Microenvironmental Niche in Tumorigenesis and Targeted Therapy, 3 Avenue Molière, 67200 Strasbourg, France
- Yundan Jia
- Inserm U1109, MN3T Team, The Microenvironmental Niche in Tumorigenesis and Targeted Therapy, 3 Avenue Molière, 67200 Strasbourg, France
- Isabelle Gasser
- Inserm U1109, MN3T Team, The Microenvironmental Niche in Tumorigenesis and Targeted Therapy, 3 Avenue Molière, 67200 Strasbourg, France
- Caroline Spenlé
- Inserm U1109, MN3T Team, The Microenvironmental Niche in Tumorigenesis and Targeted Therapy, 3 Avenue Molière, 67200 Strasbourg, France
- Benoit Langlois
- Inserm U1109, MN3T Team, The Microenvironmental Niche in Tumorigenesis and Targeted Therapy, 3 Avenue Molière, 67200 Strasbourg, France
- Martial Kammerer
- Inserm U1109, MN3T Team, The Microenvironmental Niche in Tumorigenesis and Targeted Therapy, 3 Avenue Molière, 67200 Strasbourg, France
- Olivier Lefebvre
- Inserm U1109, MN3T Team, The Microenvironmental Niche in Tumorigenesis and Targeted Therapy, 3 Avenue Molière, 67200 Strasbourg, France
- Ruslan Hlushchuk
- Institute of Anatomy, University of Bern, Baltzerstrasse 2, 3000 Bern, Switzerland
- Tristan Rupp
- Inserm U1109, MN3T Team, The Microenvironmental Niche in Tumorigenesis and Targeted Therapy, 3 Avenue Molière, 67200 Strasbourg, France
- Marija Marko
- Inserm U1109, MN3T Team, The Microenvironmental Niche in Tumorigenesis and Targeted Therapy, 3 Avenue Molière, 67200 Strasbourg, France
- Michael van der Heyden
- Inserm U1109, MN3T Team, The Microenvironmental Niche in Tumorigenesis and Targeted Therapy, 3 Avenue Molière, 67200 Strasbourg, France
- Gérard Cremel
- Inserm U1109, MN3T Team, The Microenvironmental Niche in Tumorigenesis and Targeted Therapy, 3 Avenue Molière, 67200 Strasbourg, France
- Christiane Arnold
- Inserm U1109, MN3T Team, The Microenvironmental Niche in Tumorigenesis and Targeted Therapy, 3 Avenue Molière, 67200 Strasbourg, France
- Annick Klein
- Inserm U1109, MN3T Team, The Microenvironmental Niche in Tumorigenesis and Targeted Therapy, 3 Avenue Molière, 67200 Strasbourg, France
- Patricia Simon-Assmann
- Inserm U1109, MN3T Team, The Microenvironmental Niche in Tumorigenesis and Targeted Therapy, 3 Avenue Molière, 67200 Strasbourg, France
- Valentin Djonov
- Institute of Anatomy, University of Bern, Baltzerstrasse 2, 3000 Bern, Switzerland
- Agnès Neuville-Méchine
- Hospital Hautepierre, Department of Anatomy and Pathology, 1 Avenue Molière, 67200 Strasbourg, France
- Irene Esposito
- Institute of Pathology and Anatomy, Technical University Munich, Trogerstrasse 18, 81675 München, Germany
- Julia Slotta-Huspenina
- Institute of Pathology and Anatomy, Technical University Munich, Trogerstrasse 18, 81675 München, Germany
- Klaus-Peter Janssen
- Department of Surgery Technical University Munich, Ismaningerstrasse 22, 81675 München, Germany
- Olivier de Wever
- Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium
- Gerhard Christofori
- Institute of Biochemistry and Genetics, Department of Biomedicine, University of Basel, Switzerland, Tumor Biology Team, Mattenstraße 28, 4058 Basel, Switzerland
- Thomas Hussenet
- Inserm U1109, MN3T Team, The Microenvironmental Niche in Tumorigenesis and Targeted Therapy, 3 Avenue Molière, 67200 Strasbourg, France
- Gertraud Orend
- Inserm U1109, MN3T Team, The Microenvironmental Niche in Tumorigenesis and Targeted Therapy, 3 Avenue Molière, 67200 Strasbourg, France
- DOI
- https://doi.org/10.1016/j.celrep.2013.09.014
- Journal volume & issue
-
Vol. 5,
no. 2
pp. 482 – 492
Abstract
The extracellular matrix molecule tenascin-C (TNC) is a major component of the cancer-specific matrix, and high TNC expression is linked to poor prognosis in several cancers. To provide a comprehensive understanding of TNC’s functions in cancer, we established an immune-competent transgenic mouse model of pancreatic β-cell carcinogenesis with varying levels of TNC expression and compared stochastic neuroendocrine tumor formation in abundance or absence of TNC. We show that TNC promotes tumor cell survival, the angiogenic switch, more and leaky vessels, carcinoma progression, and lung micrometastasis. TNC downregulates Dickkopf-1 (DKK1) promoter activity through the blocking of actin stress fiber formation, activates Wnt signaling, and induces Wnt target genes in tumor and endothelial cells. Our results implicate DKK1 downregulation as an important mechanism underlying TNC-enhanced tumor progression through the provision of a proangiogenic tumor microenvironment.
