The matricellular protein CYR61 interferes with normal pancreatic islets architecture and promotes pancreatic neuroendocrine tumor progression

Huang, Yu-Ting; Lan, Qiang; Ponsonnet, Lionel; Blanquet, Marisa; Christofori, Gerhard; Zaric, Jelena; Rüegg, Curzio

doi:10.18632/oncotarget.6411

Back

Journal article

+ 1 other files

The matricellular protein CYR61 interferes with normal pancreatic islets architecture and promotes pancreatic neuroendocrine tumor progression

Huang, Yu-Ting Department of Medicine, Faculty of Science, University of Fribourg, Switzerland - National Center for Competence in Research (NCCR), Molecular Oncology, Swiss Institute for Experimental Cancer Research (ISREC)-Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland
Lan, Qiang Department of Medicine, Faculty of Science, University of Fribourg, Switzerland - National Center for Competence in Research (NCCR), Molecular Oncology, Swiss Institute for Experimental Cancer Research (ISREC)-Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland
Ponsonnet, Lionel Department of Medicine, Faculty of Science, University of Fribourg, Switzerland - National Center for Competence in Research (NCCR), Molecular Oncology, Swiss Institute for Experimental Cancer Research (ISREC)-Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland
Blanquet, Marisa Department of Medicine, Faculty of Science, University of Fribourg, Switzerland
Christofori, Gerhard National Center for Competence in Research (NCCR), Molecular Oncology, Swiss Institute for Experimental Cancer Research (ISREC)-Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland - Department of Biomedicine, University of Basel, Basel, Switzerland
Zaric, Jelena Department of Medicine, Faculty of Science, University of Fribourg, Switzerland - National Center for Competence in Research (NCCR), Molecular Oncology, Swiss Institute for Experimental Cancer Research (ISREC)-Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland
Rüegg, Curzio Department of Medicine, Faculty of Science, University of Fribourg, Switzerland - National Center for Competence in Research (NCCR), Molecular Oncology, Swiss Institute for Experimental Cancer Research (ISREC)-Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland

27.11.2015

Published in:

Oncotarget. - 2015, vol. 7, no. 2, p. 1663–1674

English The significance of matricellular proteins during development and cancer progression is widely recognized. However, how these proteins actively contribute to physiological development and pathological cancer progression is only partially elucidated. In this study, we investigated the role of the matricellular protein Cysteine-rich 61 (CYR61) in pancreatic islet development and carcinogenesis. Transgenic expression of CYR61 in β cells (Rip1CYR mice) caused irregular islets morphology and distorted sorting of α cells, but did not alter islets size, number or vascularization. To investigate the function of CYR61 during carcinogenesis, we crossed Rip1CYR mice with Rip1Tag2 mice, a well-established model of β cell carcinogenesis. Beta tumors in Rip1Tag2CYR mice were larger, more invasive and more vascularized compared to tumors in Rip1Tag2 mice. The effect of CYR61 on angiogenesis was fully abrogated by treating mice with the anti-VEGFR2 mAb DC101. Results from in vitro assays demonstrated that CYR61 modulated integrin α₆β₁-dependent invasion and adhesion without altering its expression. Taken together, these results show that CYR61 expression in pancreatic β cells interferes with normal islet architecture, promotes islet tumor growth, invasion and VEGF/VERGFR-2-dependent tumor angiogenesis. Taken together, these observations demonstrate that CYR61 acts as a tumor-promoting gene in pancreatic neuroendocrine tumors.

Faculty

Faculté des sciences et de médecine

Department

Médecine 3ème année

Language