The angiostatic molecule Multimerin 2 is processed by MMP-9 to allow sprouting angiogenesis
| Autor: | Eva Andreuzzi, Rosanna Pellicani, Benedetta Bussolati, Paola Spessotto, Alessia Brossa, Paolo De Paoli, Maurizio Mongiat, Roberta Colladel, Renato Cannizzaro, Alfonso Colombatti, Giulia Tarticchio, Renato V. Iozzo, Vincenzo Canzonieri |
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| Přispěvatelé: | Andreuzzi, Eva, Colladel, Roberta, Pellicani, Rosanna, Tarticchio, Giulia, Cannizzaro, Renato, Spessotto, Paola, Bussolati, Benedetta, Brossa, Alessia, De Paoli, Paolo, Canzonieri, Vincenzo, Iozzo, Renato V., Colombatti, Alfonso, Mongiat, Maurizio |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Angiogenesis Endothelial cells Down-Regulation Neovascularization Physiologic Biology Matrix metalloproteinase Tumor microenvironment Molecular Biology Cell Line Extracellular matrix 03 medical and health sciences Endothelial cell Cell Movement medicine Biomarkers Tumor Human Umbilical Vein Endothelial Cells Humans Pseudopodia Receptor Sprouting angiogenesis Membrane Glycoproteins Neovascularization Pathologic Cell biology Endothelial stem cell Gene Expression Regulation Neoplastic Angiogenesi Vascular endothelial growth factor A 030104 developmental biology Matrix Metalloproteinase 9 Antigens Surface Proteolysis Matrix Metalloproteinase 2 HT29 Cells |
| Popis: | Angiogenesis is a crucial process occurring under physiological and pathological conditions, including cancer. The development of blood vessels is tightly regulated by a plethora of cytokines, endothelial cell (EC) receptors and extracellular matrix (ECM) components. In this context, we have shown that Multimerin 2 (MMRN2), an ECM molecule specifically secreted by ECs, exerts angiostatic functions by binding VEGFA and other pro-angiogenic cytokines. Here, we demonstrate that during angiogenic stimuli MMRN2 mRNA levels significantly decrease. Furthermore, we provide evidence that MMRN2 is processed by matrix metalloproteinases (MMPs) including MMP-9 and, to a lesser degree, by MMP-2. This proteolytic cleavage correlates with an increased migration of ECs. Accordingly, MMRN2 down-regulation is associated with an increased number of EC pseudopodia at the migrating front and this effect is attenuated using specific MMP-9 inhibitors. The down-modulation of MMRN2 occurs also in the context of tumor-associated angiogenesis. Immunofluorescence performed on tumor sections indicate a broad co-localization of MMP-9 and MMRN2, suggesting that the molecule may be extensively remodeled during tumor angiogenesis. Given the altered expression in tumors and the key role of MMRN2 in blood vessel function, we postulate that analyses of its expression may serve as a marker to predict the efficacy of the treatments. In conclusion, these data further support the role of MMRN2 as a key molecule regulating EC function and sprouting angiogenesis. (C) 2017 Published by Elsevier B.V. |
| Databáze: | OpenAIRE |
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