Lost in disruption: Role of proteases in glioma invasion and progression
Abstract
A characteristic feature of malignant glial tumors (gliomas) is their tendency to diffusely infiltrate the nervous system preventing their complete surgical resection. Proteases play a decisive role in this malignant process, either by degradation of brain extracellular matrix (ECM) components, adhesion molecules, or by regulating the activity of growth and chemotactic factors. Secreted matrix metalloproteinases (MMPs) and ADAMTS proteases (ADAMs with thrombospondin motifs) cleave different ECM components like the proteoglycans (lecticans) aggrecan, versican, neurocan and brevican with selective preferences; they are further regulated by endogenous inhibitors and activating metallo- and serine proteases. Cell surface proteases of the ADAM family (A Disintegrin And Metalloproteinase), but also serine proteases regulate the activity of growth factors and chemokines that act as autocrine / paracrine stimulators within gliomas. Thus, proteases play a decisive role for the spread and growth of gliomas and are prominent targets for their therapy.
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Gliomas release several ECM remodeling/degrading enzymes including MMPs, for which PNN proteoglycans are known substrates.
“Gliomas release several ECM remodeling/degrading enzymes28 including MMPs29, for which PNN proteoglycans are known substrates21”
From Perineuronal nets decrease membrane capacitance of peritumoral fast spiking interneurons in a model of epilepsy (2018) · cites this paper as [21]
PNN constituents are substrates for matrix degrading enzymes including MMPs, ADAMs, and ADAMTs, which are known to be released from gliomas.
“Interestingly, PNNs constituents are also substrates for matrix degrading enzymes including matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase (ADAMs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTs), which are known to be released from gliomas21”
From Perineuronal nets decrease membrane capacitance of peritumoral fast spiking interneurons in a model of epilepsy (2018) · cites this paper as [21]
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Hemodynamic molecular imaging of tumor-associated enzyme activity in the living brainPreprint
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- Authors
- Mentlein, R., Hattermann, K., & Held-Feindt, J.
- Affiliations
- Christian-Albrechts-Universität zu Kiel (DE)
- Corresponding author
- Mentlein, Rolf
- Venue
- Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
- Publisher
- Elsevier BV
- Published
- 2012-04
- Volume
- 1825
- Issue
- 2
- Pages
- 178-185
- ISSN
- 0304-419X (ISSN-L)
- OpenAlex
- W2023393975
- Cited by
- 85
- References
- 96
- Citations by year
- 2025: 4 · 2024: 4 · 2023: 9 · 2022: 4 · 2021: 12 · 2020: 7 · 2019: 5 · 2018: 8 · 2017: 3 · 2016: 7 · 2015: 6 · 2014: 7 · 2013: 7 · 2012: 2
- FWCI
- 0.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochimica et Biophysica Acta (BBA) - Reviews on Cancer (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Peptidase Inhibition and Analysis
- Keywords
- glioma, proteolytic enzymes, tumor invasion, tumor progression, matrix metalloproteinases, ADAMTS proteases, ADAM family, extracellular matrix degradation, proteoglycans, aggrecan, versican, neurocan, brevican, serine protease, growth factor activation, chemokines, autocrine and paracrine signaling, protease inhibitors, glioma treatment
- MeSH terms
- Animals, Brain Neoplasms, Glioma, Humans, Neoplasm Invasiveness, Peptide Hydrolases, Disease Progression
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