| Dokumentenart: | Artikel | ||||||||||||||||||||||||||||||||||||||||
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| Titel eines Journals oder einer Zeitschrift: | Neuro-oncology | ||||||||||||||||||||||||||||||||||||||||
| Verlag: | Oxford Univ. Press | ||||||||||||||||||||||||||||||||||||||||
| Band: | 11 | ||||||||||||||||||||||||||||||||||||||||
| Nummer des Zeitschriftenheftes oder des Kapitels: | 4 | ||||||||||||||||||||||||||||||||||||||||
| Seitenbereich: | S. 368-380 | ||||||||||||||||||||||||||||||||||||||||
| Datum: | 2009 | ||||||||||||||||||||||||||||||||||||||||
| Institutionen: | Medizin > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) Medizin > Zentren des Universitätsklinikums Regensburg > Zentrum für Hirntumore (ZHT) | ||||||||||||||||||||||||||||||||||||||||
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| Dewey-Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||||||||||||||||||||||||||||||||||||||
| Status: | Veröffentlicht | ||||||||||||||||||||||||||||||||||||||||
| Begutachtet: | Ja, diese Version wurde begutachtet | ||||||||||||||||||||||||||||||||||||||||
| An der Universität Regensburg entstanden: | Unbekannt / Keine Angabe | ||||||||||||||||||||||||||||||||||||||||
| Dokumenten-ID: | 29313 |
Zusammenfassung
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 ...
Zusammenfassung
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.
Metadaten zuletzt geändert: 29 Sep 2021 07:39
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