The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Lactate promotes glioma migration by TGF-β2–dependent regulation of matrix metalloproteinase-2
Open accessAbstract
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.
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Cites
Fantin, V. R., St-Pierre, J., & Leder, P. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.04.023 · Cited by 1,635
Acid-Mediated Tumor Invasion: a Multidisciplinary Study
Gatenby, R. A., Gawlinski, E. T., Gmitro, A. F., Kaylor, B., & Gillies, R. J. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-4193 · Cited by 771
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Lactate modulation of immune responses in inflammatory versus tumour microenvironments
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Eelen, G., de Zeeuw, P., Treps, L., Harjes, U., Wong, B. W., & Carmeliet, P. (2018) · Physiological Reviews · doi:10.1152/physrev.00001.2017 · Cited by 572
Metadata
- Authors
- Baumann, F., Leukel, P., Doerfelt, A., Beier, C. P., Dettmer, K., Oefner, P. J., Kastenberger, M., Kreutz, M., Nickl-Jockschat, T., Bogdahn, U., Bosserhoff, A.-K., & Hau, P.
- Venue
- Neuro-Oncology
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-08-01
- Volume
- 11
- Issue
- 4
- Pages
- 368-380
- ISSN
- 1522-8517 (ISSN-L)
- 1523-5866
- OpenAlex
- W2064972175
- Cited by
- 256
- References
- 2
- FWCI
- 1.92
- Type
- journal article
- Language
- en
- Open access
- green
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- Baumann, F., Leukel, P., Doerfelt, A., Beier, C. P., Dettmer, K., Oefner, P. J., Kastenberger, M., Kreutz, M., Nickl-Jockschat, T., Bogdahn, U., Bosserhoff, A.-K., & Hau, P. (2009). Lactate promotes glioma migration by TGF-β2–dependent regulation of matrix metalloproteinase-2. Neuro-Oncology. https://doi.org/10.1215/15228517-2008-106
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