Baumann, Fusun and Leukel, Petra and Doerfelt, Anett and Beier, Christoph P. and Dettmer, Katja and Oefner, Peter J. and Kastenberger, Michael and Kreutz, Marina and Nickl-Jockschat, Thomas and Bogdahn, Ulrich and Bosserhoff, Anja-Katrin and Hau, Peter (2009) Lactate promotes glioma migration by TGF-beta 2-dependent regulation of matrix metalloproteinase-2. NEURO-ONCOLOGY, 11 (4). pp. 368-380. ISSN 1522-8517, 1523-5866
Full text not available from this repository. (Request a copy)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-beta 2 (TGF-beta 2) 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-beta 2-mediated migration of glioma cells. Small interfering RNA directed against LDH-A (siLDHA) suppresses, and lactate induces, TGF-beta 2 expression, suggesting that lactate metabolism is strongly associated with TGF-beta 2 in glioma cells. Here we demonstrate that TGF-beta 2 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 avb3 abrogated glioma cell migration stimulated by TGF-beta 2. Furthermore, siLDH-A inhibited MMP2 activity, leading to inhibition of glioma migration. Taken together, we define an LDH-A-induced and TGF-beta 2-coordinated regulatory cascade of transcriptional regulation of MMP-2 and integrin alpha(v)beta(3). This novel interaction between lactate metabolism and TGF-beta 2 might constitute a crucial mechanism for glioma migration. Neuro-Oncology 11, 368-380, 2009 (Posted to Neuro-Oncology [serial online], Doc. D08-00206, November 25, 2008. URL http://neuro-oncology.dukejournals.org; DOI: 10.1215/15228517-2008-106)
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GROWTH-FACTOR-BETA; BRAIN-TUMOR CELLS; TRANSFORMING GROWTH-FACTOR-BETA-2; INTEGRIN ALPHA-V-BETA-3; MALIGNANT GLIOMAS; UP-REGULATION; GELATINASE-A; TGF-BETA; IN-VIVO; INVASION; glioma; lactate; LDH-A; MMP-2; TGF-beta 2 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Neurologie Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Sep 2020 08:26 |
| Last Modified: | 10 Sep 2020 08:26 |
| URI: | https://pred.uni-regensburg.de/id/eprint/28659 |
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