Transglutaminase 2 expression is increased as a function of malignancy grade and negatively regulates cell growth in meningioma

Yin-Cheng Huang; Kuo-Chen Wei; Chen-Nen Chang; Pin-Yuan Chen; Peng-Wei Hsu; Carl P Chen; Chin-Song Lu; Hung-Li Wang; David H Gutmann; Tu-Hsueh Yeh

doi:10.1371/journal.pone.0108228

Transglutaminase 2 expression is increased as a function of malignancy grade and negatively regulates cell growth in meningioma

PLoS One. 2014 Sep 23;9(9):e108228. doi: 10.1371/journal.pone.0108228. eCollection 2014.

Authors

Affiliations

¹ Department of Neurosurgery, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Chang Gung University, College of Medicine, Taoyuan, Taiwan.
² Department of Rehabilitation, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Chang Gung University, College of Medicine, Taoyuan, Taiwan.
³ Department of Neurology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Chang Gung University, College of Medicine, Taoyuan, Taiwan.
⁴ Chang Gung University, College of Medicine, Taoyuan, Taiwan.
⁵ Department of Neurology, Washington University, School of Medicine, St. Louis, Missouri, United States of America.

Abstract

Most meningiomas are benign, but some clinical-aggressive tumors exhibit brain invasion and cannot be resected without significant complications. To identify molecular markers for these clinically-aggressive meningiomas, we performed microarray analyses on 24 primary cultures from 21 meningiomas and 3 arachnoid membranes. Using this approach, increased transglutaminase 2 (TGM2) expression was observed, which was subsequently validated in an independent set of 82 meningiomas by immunohistochemistry. Importantly, the TGM2 expression level was associated with increasing WHO malignancy grade as well as meningioma recurrence. Inhibition of TGM2 function by siRNA or cystamine induced meningioma cell death, which was associated with reduced AKT phosphorylation and caspase-3 activation. Collectively, these findings suggest that TGM2 expression increases as a function of malignancy grade and tumor recurrence and that inhibition of TGM2 reduces meningioma cell growth.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Caspase 3 / metabolism
Cell Death / physiology
GTP-Binding Proteins / genetics
GTP-Binding Proteins / metabolism*
Humans
Meningeal Neoplasms / enzymology*
Meningeal Neoplasms / pathology
Meningioma / enzymology*
Meningioma / pathology
Neoplasm Grading
Protein Glutamine gamma Glutamyltransferase 2
Proto-Oncogene Proteins c-akt / metabolism
Transglutaminases / genetics
Transglutaminases / metabolism*

Substances

TGM2 protein, human
Protein Glutamine gamma Glutamyltransferase 2
Transglutaminases
Proto-Oncogene Proteins c-akt
Caspase 3
GTP-Binding Proteins

Grants and funding

This work was supported by the National Science Council Taiwan (NSC 100-2314-B-182A-015-MY3 to Y.H.; NSC 100-2321-B-182A-001- to T.Y.) and the Chang Gung Medical Foundation Taiwan (grant number CMRPG392052 to Y.H.; CMRPG392201 to T.Y.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.