University of Hertfordshire

From the same journal

By the same authors


  • Pinar Uysal-Onganer
  • Amy MacLatchy
  • Rayan Mahmoud
  • Igor Kraev
  • Paul R Thompson
  • Jameel Inal
  • Sigrun Lange
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Original languageEnglish
Article number1495
Number of pages29
JournalInternational Journal of Molecular Sciences
Publication statusPublished - 22 Feb 2020


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.


Funding Information: Funding: This work was supported in parts by a University of Westminster Start-up Grants to S.L. and P.U.-O. Funding Information: Acknowledgments: The authors would like to thank Yagnesh Umrania and Michael Deery at the Cambridge Centre for Proteomics for the LC-MS/MS analysis. Thanks are due to The Guy Foundation for funding the purchase of equipment utilised in this work. Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

ID: 19869944