Journal article
Lactate promotes glioma migration by TGF-β2–dependent regulation of matrix metalloproteinase-2
Neuro-oncology (Charlottesville, Va.), Vol.11(4), pp.368-380
08/2009
DOI: 10.1215/15228517-2008-106
PMCID: PMC2743217
PMID: 19033423
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-β2 (TGF-β2) 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-β2–mediated migration of glioma cells. Small interfering RNA directed against LDH-A (siLDH-A) suppresses, and lactate induces, TGF-β2 expression, suggesting that lactate metabolism is strongly associated with TGF-β2 in glioma cells. Here we demonstrate that TGF-β2 enhances expression, secretion, and activation of matrix metalloproteinase-2 (MMP-2) and induces the cell surface expression of integrin α
v
β
3
receptors. In spheroid and Boyden chamber migration assays, inhibition of MMP-2 activity using a specific MMP-2 inhibitor and blocking of integrin α
v
β
3
abrogated glioma cell migration stimulated by TGF-β2. Furthermore, siLDH-A inhibited MMP2 activity, leading to inhibition of glioma migration. Taken together, we define an LDH-A–induced and TGF-β2–coordinated regulatory cascade of transcriptional regulation of MMP-2 and integrin α
v
β
3
. This novel interaction between lactate metabolism and TGF-β2 might constitute a crucial mechanism for glioma migration.
Details
- Title: Subtitle
- Lactate promotes glioma migration by TGF-β2–dependent regulation of matrix metalloproteinase-2
- Creators
- Fusun BaumannPetra LeukelAnett DoerfeltChristoph P BeierKatja DettmerPeter J OefnerMichael KastenbergerMarina KreutzThomas Nickl-JockschatUlrich BogdahnAnja-Katrin BosserhoffPeter Hau
- Resource Type
- Journal article
- Publication Details
- Neuro-oncology (Charlottesville, Va.), Vol.11(4), pp.368-380
- DOI
- 10.1215/15228517-2008-106
- PMID
- 19033423
- PMCID
- PMC2743217
- NLM abbreviation
- Neuro Oncol
- ISSN
- 1522-8517
- eISSN
- 1523-5866
- Publisher
- Duke University Press
- Language
- English
- Date published
- 08/2009
- Academic Unit
- Psychiatry; Neuroscience and Pharmacology
- Record Identifier
- 9984004077302771
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