| Item type: | Article | ||||||||||||||||||||||||||||||||||||||||
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| Journal or Publication Title: | Neuro-oncology | ||||||||||||||||||||||||||||||||||||||||
| Publisher: | Oxford Univ. Press | ||||||||||||||||||||||||||||||||||||||||
| Volume: | 11 | ||||||||||||||||||||||||||||||||||||||||
| Number of Issue or Book Chapter: | 4 | ||||||||||||||||||||||||||||||||||||||||
| Page Range: | pp. 368-380 | ||||||||||||||||||||||||||||||||||||||||
| Date: | 2009 | ||||||||||||||||||||||||||||||||||||||||
| Institutions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) Medicine > Zentren des Universitätsklinikums Regensburg > Zentrum für Hirntumore (ZHT) | ||||||||||||||||||||||||||||||||||||||||
| Identification Number: |
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| Classification: |
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| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||||||||||||||||||||||||||||||||||||||
| Status: | Published | ||||||||||||||||||||||||||||||||||||||||
| Refereed: | Yes, this version has been refereed | ||||||||||||||||||||||||||||||||||||||||
| Created at the University of Regensburg: | Unknown | ||||||||||||||||||||||||||||||||||||||||
| Item ID: | 29313 |
Abstract
Lactate dehydrogenase type A (LDH-A) is a key metabolic enzyme catalyzing pyruvate into lactate and is excessively expressed by tumor cells. Transforming growth factor-beta2 (TGF-beta2) is a key regulator of invasion in high-grade gliomas, partially by inducing a mesenchymal phenotype and by remodeling the extracellular matrix. In this study, we tested the hypothesis that lactate metabolism ...
Abstract
Lactate dehydrogenase type A (LDH-A) is a key metabolic enzyme catalyzing pyruvate into lactate and is excessively expressed by tumor cells. Transforming growth factor-beta2 (TGF-beta2) is a key regulator of invasion in high-grade gliomas, partially by inducing a mesenchymal phenotype and by remodeling the extracellular matrix. In this study, we tested the hypothesis that lactate metabolism regulates TGF-beta2-mediated migration of glioma cells. Small interfering RNA directed against LDH-A (siLDH-A) suppresses, and lactate induces, TGF-beta2 expression, suggesting that lactate metabolism is strongly associated with TGF-beta2 in glioma cells. Here we demonstrate that TGF-beta2 enhances expression, secretion, and activation of matrix metalloproteinase-2 (MMP-2) and induces the cell surface expression of integrin alpha(v)beta(3) receptors. In spheroid and Boyden chamber migration assays, inhibition of MMP-2 activity using a specific MMP-2 inhibitor and blocking of integrin alpha(v)beta(3) abrogated glioma cell migration stimulated by TGF-beta2. Furthermore, siLDH-A inhibited MMP2 activity, leading to inhibition of glioma migration. Taken together, we define an LDH-A-induced and TGF-beta2-coordinated regulatory cascade of transcriptional regulation of MMP-2 and integrin alpha(v)beta(3). This novel interaction between lactate metabolism and TGF-beta2 might constitute a crucial mechanism for glioma migration.
Metadata last modified: 25 May 2018 13:05
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