The matricellular protein CYR61 interferes with normal pancreatic islets architecture and promotes pancreatic neuroendocrine tumor progression
| Autor: | Marisa Blanquet, Curzio Rüegg, Lionel Ponsonnet, Jelena Zaric, Gerhard Christofori, Qiang Lan, Yu-Ting Huang |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Angiogenesis Blotting Western Mice Transgenic Biology Neuroendocrine tumors insulinoma medicine.disease_cause 03 medical and health sciences angiogenesis Islets of Langerhans Internal medicine Cell Line Tumor medicine Animals Insulinoma geography geography.geographical_feature_category Integrin alpha6beta1 Neovascularization Pathologic Reverse Transcriptase Polymerase Chain Reaction Pancreatic islets Matricellular protein CYR61 GTPase-Activating Proteins Antibodies Monoclonal medicine.disease Islet invasion Vascular Endothelial Growth Factor Receptor-2 Mice Inbred C57BL Pancreatic Neoplasms Neuroendocrine Tumors 030104 developmental biology Endocrinology medicine.anatomical_structure Cell Transformation Neoplastic Oncology transgenic model Cancer research Disease Progression Carcinogenesis Research Paper Cysteine-Rich Protein 61 |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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