Current insights into matrix metalloproteinases and glioma progression: transcending the degradation boundary
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Abstract: Glioblastoma multiforme (GBM) remains one of the most deadly cancers, with modest advances in overall survival despite significant improvements in imaging, surgery, and molecular genomic understanding. The highest-grade glioma, GBM is a primary brain cancer that is molecularly heterogeneous among patients and even within the same patient. Key hallmarks include glioma-cell invasion, angiogenesis, and therapeutic resistance. While once considered a major player in glioma invasion, members of the MMP family are also associated with other key pathological hallmarks of glioma. Investigations into understanding MMP function in GBM were slowed due to the failed MMP-inhibitor trials for GBM in the 2000s. In contrast, the field of MMPs in other brain pathologies has flourished in such areas as traumatic brain injury, multiple sclerosis, and stroke. In the past decade, the increase in publicly available data sets documenting patient-biopsy molecular information has empowered laboratory investigations into the spectrum of genomic, transcriptomic, and proteomic changes associated with glioma, including MMPs. In this review, we selected one of these data sets to illustrate a small sample of information that can be obtained from such analyses. Combined with recent reports on the use of MMP-cleavable peptides for imaging and the multifunctionality of MMPs, including intracellular nonproteolytic actions in various cell types, this paves the way for new avenues of MMP research. Understanding the function of MMPs in host–tumor interactions both spatially and temporally during tumor progression and in response to treatment will be crucial for the advancement of targeting specific MMPs in GBM. The opportunities to explore MMP regulation, expression, and function further in GBM have never been so great with progress in modern bioinformatics and molecular techniques, and it is hoped that advancements will translate in some way to patients diagnosed with GBM.
Date Issued
2018-09-17
Date Acceptance
2018-06-11
Citation
Metalloproteinases In Medicine, 2018, 2018 (5), pp.13-30
Publisher
Dove Medical Press Ltd.
Start Page
13
End Page
30
Journal / Book Title
Metalloproteinases In Medicine
Volume
2018
Issue
5
Copyright Statement
© 2018 Pullen et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.
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permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php)
php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work
you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For
permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php)
Identifier
https://www.dovepress.com/current-insights-into-matrix-metalloproteinases-and-glioma-progression-peer-reviewed-article-MNM
Publication Status
Published online
Date Publish Online
2018-09-17