MULTIMERIN2 binds VEGF-A primarily via the carbohydrate chains exerting an angiostatic function and impairing tumor growth
| Autor: | F. Todaro, Eva Andreuzzi, Alfonso Colombatti, Giulia Tarticchio, Roberta Colladel, Alice Paulitti, Maurizio Mongiat, Rosanna Pellicani |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Vascular Endothelial Growth Factor A Glycosylation Angiogenesis endothelial cell sprouting Fibrosarcoma Carbohydrates Fluorescent Antibody Technique Mice Nude Apoptosis Biology Real-Time Polymerase Chain Reaction vascular endothelial growth factor (VEGF) Extracellular matrix Immunoenzyme Techniques 03 medical and health sciences angiogenesis Mice Cell Movement Human Umbilical Vein Endothelial Cells Tumor Cells Cultured tumor microenvironment Animals Humans RNA Messenger Phosphorylation Receptor Cell Proliferation Tumor microenvironment Mice Inbred BALB C Membrane Glycoproteins Neovascularization Pathologic Cell growth Reverse Transcriptase Polymerase Chain Reaction Surface Plasmon Resonance extracellular matrix (ECM) Xenograft Model Antitumor Assays Cell biology Vascular endothelial growth factor A 030104 developmental biology Oncology Biochemistry Antigens Surface Ectopic expression Female Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | Angiogenesis is a key process occurring under both physiological and pathological conditions and is a hallmark of cancer. We have recently demonstrated that the extracellular matrix (ECM) molecule MULTIMERIN2 exerts an angiostatic function through the binding to VEGF-A. In this study we identify the region of the molecule responsible for the binding and demonstrate that the interaction involves the carbohydrate chains. MULTIMERIN2 interacts with other VEGF-A isoforms and VEGF family members such as VEGF-B, -C, -D and PlGF-1 suggesting that the molecule may function as a reservoir for different cytokines. In response to VEGF-A165, we show that MULTIMERIN2 impairs the phosphorylation of VEGFR2 at both Y1175 and Y1214 residues, halts SAPK2/p38 activation and negatively affects endothelial cell motility. In addition, MULTIMERIN2 and its active deletion mutant decrease the availability of the VEGFR2 receptor at the EC plasma membrane. The ectopic expression of MULTIMERIN2 or its active deletion mutant led to a striking reduction of tumor-associated angiogenesis and tumor growth. In conclusion, these data pinpoint MULTIMERIN2 as a key angiostatic molecule and disclose the possibility to develop new prognostic tools and improve the management of cancer patients. |
| Databáze: | OpenAIRE |
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