Peptidylarginine Deiminase Isozyme-Specific PAD2, PAD3 and PAD4 Inhibitors Differentially Modulate Extracellular Vesicle Signatures and Cell Invasion in Two Glioblastoma Multiforme Cell Lines
Authors
Uysal-Onganer, PinarMacLatchy, Amy
Mahmoud, Rayan
Kraev, Igor
Thompson, Paul R
Inal, Jameel M.
Lange, Sigrun
Document Type
Journal ArticlePublication Date
2020-02-22Keywords
HIF-1Stromal interaction molecule 1 (STIM-1)
extracellular vesicles (EVs)
glioblastoma multiforme (GBM)
microRNA (miR21
miR126
miR210)
moesin
peptidylarginine deiminases (PADs)
prohibitin (PHB)
protein deimination
Amino Acids, Peptides, and Proteins
Biochemistry
Cancer Biology
Cell Biology
Cells
Enzymes and Coenzymes
Molecular Biology
Neoplasms
Nucleic Acids, Nucleotides, and Nucleosides
Metadata
Show full item recordAbstract
Glioblastoma multiforme (GBM) is an aggressive adult brain tumour with poor prognosis. Roles for peptidylarginine deiminases (PADs) in GBM have recently been highlighted. Here, two GBM cell lines were treated with PAD2, PAD3 and PAD4 isozyme-specific inhibitors. Effects were assessed on extracellular vesicle (EV) signatures, including EV-microRNA cargo (miR21, miR126 and miR210), and on changes in cellular protein expression relevant for mitochondrial housekeeping (prohibitin (PHB)) and cancer progression (stromal interaction molecule 1 (STIM-1) and moesin), as well as assessing cell invasion. Overall, GBM cell-line specific differences for the three PAD isozyme-specific inhibitors were observed on modulation of EV-signatures, PHB, STIM-1 and moesin protein levels, as well as on cell invasion. The PAD3 inhibitor was most effective in modulating EVs to anti-oncogenic signatures (reduced miR21 and miR210, and elevated miR126), to reduce cell invasion and to modulate protein expression of pro-GBM proteins in LN229 cells, while the PAD2 and PAD4 inhibitors were more effective in LN18 cells. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for deiminated proteins relating to cancer, metabolism and inflammation differed between the two GBM cell lines. Our findings highlight roles for the different PAD isozymes in the heterogeneity of GBM tumours and the potential for tailored PAD-isozyme specific treatment.Source
Uysal-Onganer P, MacLatchy A, Mahmoud R, Kraev I, Thompson PR, Inal JM, Lange S. Peptidylarginine Deiminase Isozyme-Specific PAD2, PAD3 and PAD4 Inhibitors Differentially Modulate Extracellular Vesicle Signatures and Cell Invasion in Two Glioblastoma Multiforme Cell Lines. Int J Mol Sci. 2020 Feb 22;21(4):1495. doi: 10.3390/ijms21041495. PMID: 32098295. Link to article on publisher's site
DOI
10.3390/ijms21041495Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41377PubMed ID
32098295Related Resources
Rights
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.3390/ijms21041495
Scopus Count
Except where otherwise noted, this item's license is described as © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).