The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Gliomas induce and exploit microglial MT1-MMP expression for tumor expansion
Open accessAbstract
Diffuse infiltration of glioma cells into normal brain tissue is considered to be a main reason for the unfavorable outcomes of patients with malignant gliomas. Invasion of glioma cells into the brain parenchyma is facilitated by metalloprotease-mediated degradation of the extracellular matrix. Metalloproteases are released as inactive pro-forms and get activated upon cleavage by membrane bound metalloproteases. Here, we show that membrane type 1 metalloprotease (MT1-MMP) is up-regulated in glioma-associated microglia, but not in the glioma cells. Overexpression of MT1-MMP is even lethal for glioma cells. Glioma-released factors trigger the expression and activity of MT1-MMP via microglial toll-like receptors and the p38 MAPK pathway, as deletion of the toll-like receptor adapter protein MyD88 or p38 inhibition prevented MT1-MMP expression and activity in cultured microglial cells. Microglial MT1-MMP in turn activates glioma-derived pro-MMP-2 and promotes glioma expansion, as shown in an ex vivo model using MT1-MMP-deficient brain tissue and a microglia depletion paradigm. Finally, MyD88 deficiency or microglia depletion largely attenuated glioma expansion in 2 independent in vivo models.
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Cites
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Cited by
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Self-citationThe role of microglia and macrophages in glioma maintenance and progression
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Glial cells in (patho)physiology
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Microglia–blood vessel interactions: a double-edged sword in brain pathologies
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Metadata
- Authors
- Markovic, D. S., Vinnakota, K., Chirasani, S., Synowitz, M., Raguet, H., Stock, K., Sliwa, M., Lehmann, S., Kälin, R., van Rooijen, N., Holmbeck, K., Heppner, F. L., Kiwit, J., Matyash, V., Lehnardt, S., Kaminska, B., Glass, R., & Kettenmann, H.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2009-07-28
- Volume
- 106
- Issue
- 30
- Pages
- 12530-12535
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2048898424
- Cited by
- 391
- References
- 35
- FWCI
- 5.34
- Type
- journal article
- Language
- en
- Open access
- green
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- Markovic, D. S., Vinnakota, K., Chirasani, S., Synowitz, M., Raguet, H., Stock, K., Sliwa, M., Lehmann, S., Kälin, R., van Rooijen, N., Holmbeck, K., Heppner, F. L., Kiwit, J., Matyash, V., Lehnardt, S., Kaminska, B., Glass, R., & Kettenmann, H. (2009). Gliomas induce and exploit microglial MT1-MMP expression for tumor expansion. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0804273106
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
