Article
Molecular mechanisms of brain invasion in meningiomas – a systematic review
Molekulare Mechanismen der Gehirninvasion bei Meningeomen: ein systematisches Review
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Published: | May 25, 2022 |
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Outline
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Objective: Invasion of brain tissue by meningioma has been identified as one key factor for meningioma recurrence and is a stand-alone criterion for atypical meningioma (CNS WHO grade 2). While post-surgery irradiation therapy might be initiated in brain-invasive meningiomas to prevent recurrences, specific treatment approaches targeting key molecules involved in the invasive process are not established. Here we have compiled the current knowledge about mechanisms supporting brain tissue invasion by meningiomas.
Methods: A systematic search was performed in both the Embase and PubMed databases. Using the Emtree/MeSH terms, “meningioma AND invasion” as well as “meningioma AND migration” were searched. Results were merged and conference abstracts as well as non-English articles removed. The remaining titles and abstracts were then screened for relevance to this review.
Results: The initial search returned 2336 results which were narrowed down according to PRISMA guidelines to 224 full text studies and reviewed for relevance to this study. The current data suggests that the remodeling and modification of extracellular matrix proteins seems to be the dominating feature of meningioma invasion. Proteases such as MMP 9 or Cathepsin B, L were widely shown to correlate with invasive features. Similarly, Integrins, proteins involved in Cell-Cell and Cell-ECM interactions as well as cytoskeletal changes seem to contribute to the invasion process. The epithelial to mesenchymal transition (EMT) known to drive invasion in other cancers seems to have limited impact in meningioma invasion.
Conclusion: The capacity of Meningioma to invade surrounding structures with the potential consequence of worse clinical outcome represents a process which is not well understood so far. The available data are limited because most studies have used simple correlative approaches linking invasiveness with different proteins in vitro or analyzing human meningioma samples for expression. To characterize such a complex mechanism, more sophisticated methods than previously used are necessary to capture inter and intratumoral differences that may arise due to different migratory programs. Simple immunohistochemical approaches and collective protein expression analysis might not sufficiently elucidate the diverse local intratumoral expression dynamics. Single cell analyses and better models of invasion might help to further elucidate this elaborate process.
Figure 1 [Fig. 1]