SuperQuant-assisted Comparative Proteome Analysis of Glioblastoma Subpopulations Allows for Identification of Potential Novel Therapeutic Targets and Cell Markers

Overview

Journal Oncotarget

Specialty Oncology

Date 2018 Mar 7

PMID 29507698

Citations 6

Authors

Thiago Verano-Braga

Vladimir Gorshkov

Sune Munthe

Mia D Sorensen

Bjarne W Kristensen

Frank Kjeldsen

Affiliations

Soon will be listed here.

Abstract

Glioblastoma (GBM) is a highly aggressive brain cancer with poor prognosis and low survival rate. Invasive cancer stem-like cells (CSCs) are responsible for tumor recurrence because they escape current treatments. Our main goal was to study the proteome of three GBM subpopulations to identify key molecules behind GBM cell phenotypes and potential cell markers for migrating cells. We used SuperQuant-an enhanced quantitative proteome approach-to increase proteome coverage. We found 148 proteins differentially regulated in migrating CSCs and 199 proteins differentially regulated in differentiated cells. We used Ingenuity Pathway Analysis (IPA) to predict upstream regulators, downstream effects and canonical pathways associated with regulated proteins. IPA analysis predicted activation of integrin-linked kinase (ILK) signaling, actin cytoskeleton signaling, and lysine demethylase 5B (KDM5B) in CSC migration. Moreover, our data suggested that microRNA-122 (miR-122) is a potential upstream regulator of GBM phenotypes as miR-122 activation was predicted for differentiated cells while its inhibition was predicted for migrating CSCs. Finally, we validated transferrin (TF) and procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2) as potential markers for migrating cells.

Citing Articles

Application of two-dimensional difference gel electrophoresis to identify protein changes between center, margin, and adjacent non-tumor tissues obtained from non-small-cell lung cancer with adenocarcinoma or squamous cell carcinoma subtype.

Ciereszko A, Dietrich M, Slowinska M, Nynca J, Ciborowski M, Kaczmarek M PLoS One. 2022; 17(5):e0268073.

PMID: 35512017 PMC: 9071164. DOI: 10.1371/journal.pone.0268073.

Inhibitor of Hyaluronic Acid Synthesis 4-Methylumbelliferone Suppresses the Secretory Processes That Ensure the Invasion of Neutrophils into Tissues and Induce Inflammation.

Galkina S, Fedorova N, Ksenofontov A, Golenkina E, Serebryakova M, Stadnichuk V Biomedicines. 2022; 10(2).

PMID: 35203523 PMC: 8869632. DOI: 10.3390/biomedicines10020314.

Adenosinergic Signaling as a Key Modulator of the Glioma Microenvironment and Reactive Astrocytes.

Debom G, Rubenich D, Braganhol E Front Neurosci. 2022; 15:648476.

PMID: 35069091 PMC: 8766410. DOI: 10.3389/fnins.2021.648476.

Inhibition of Neutrophil Secretion Upon Adhesion as a Basis for the Anti-Inflammatory Effect of the Tricyclic Antidepressant Imipramine.

Galkina S, Golenkina E, Fedorova N, Ksenofontov A, Serebryakova M, Arifulin E Front Pharmacol. 2021; 12:709719.

PMID: 34421605 PMC: 8375473. DOI: 10.3389/fphar.2021.709719.

Neutrophil Adhesion and the Release of the Free Amino Acid Hydroxylysine.

Galkina S, Fedorova N, Ksenofontov A, Serebryakova M, Golenkina E, Stadnichuk V Cells. 2021; 10(3).

PMID: 33807594 PMC: 7999338. DOI: 10.3390/cells10030563.

References

Stupp R, Hegi M, Mason W, van den Bent M, Taphoorn M, Janzer R . Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009; 10(5):459-66. DOI: 10.1016/S1470-2045(09)70025-7. View

Kurozumi A, Kato M, Goto Y, Matsushita R, Nishikawa R, Okato A . Regulation of the collagen cross-linking enzymes LOXL2 and PLOD2 by tumor-suppressive microRNA-26a/b in renal cell carcinoma. Int J Oncol. 2016; 48(5):1837-46. PMC: 4809659. DOI: 10.3892/ijo.2016.3440. View

Miyamoto K, Seki N, Matsushita R, Yonemori M, Yoshino H, Nakagawa M . Tumour-suppressive miRNA-26a-5p and miR-26b-5p inhibit cell aggressiveness by regulating PLOD2 in bladder cancer. Br J Cancer. 2016; 115(3):354-63. PMC: 4973152. DOI: 10.1038/bjc.2016.179. View

Chang H, Sneddon J, Alizadeh A, Sood R, West R, Montgomery K . Gene expression signature of fibroblast serum response predicts human cancer progression: similarities between tumors and wounds. PLoS Biol. 2004; 2(2):E7. PMC: 314300. DOI: 10.1371/journal.pbio.0020007. View

Dong S, Nutt C, Betensky R, Stemmer-Rachamimov A, Denko N, Ligon K . Histology-based expression profiling yields novel prognostic markers in human glioblastoma. J Neuropathol Exp Neurol. 2005; 64(11):948-55. PMC: 1557632. DOI: 10.1097/01.jnen.0000186940.14779.90. View

Wang Y, Kuramitsu Y, Ueno T, Suzuki N, Yoshino S, Iizuka N . Proteomic differential display identifies upregulated vinculin as a possible biomarker of pancreatic cancer. Oncol Rep. 2012; 28(5):1845-50. DOI: 10.3892/or.2012.2004. View

Gilbert C, Ross A . Cancer stem cells: cell culture, markers, and targets for new therapies. J Cell Biochem. 2009; 108(5):1031-8. PMC: 2909872. DOI: 10.1002/jcb.22350. View

Ludwig N, Leidinger P, Becker K, Backes C, Fehlmann T, Pallasch C . Distribution of miRNA expression across human tissues. Nucleic Acids Res. 2016; 44(8):3865-77. PMC: 4856985. DOI: 10.1093/nar/gkw116. View

Taverner T, Karpievitch Y, Polpitiya A, Brown J, Dabney A, Anderson G . DanteR: an extensible R-based tool for quantitative analysis of -omics data. Bioinformatics. 2012; 28(18):2404-6. PMC: 3436848. DOI: 10.1093/bioinformatics/bts449. View

10.

Fowler A, Thomson D, Giles K, Maleki S, Mreich E, Wheeler H . miR-124a is frequently down-regulated in glioblastoma and is involved in migration and invasion. Eur J Cancer. 2011; 47(6):953-63. DOI: 10.1016/j.ejca.2010.11.026. View

11.

Gilkes D, Semenza G, Wirtz D . Hypoxia and the extracellular matrix: drivers of tumour metastasis. Nat Rev Cancer. 2014; 14(6):430-9. PMC: 4283800. DOI: 10.1038/nrc3726. View

12.

Meyer T, Brinck U . Immunohistochemical detection of vinculin in human rhabdomyosarcomas. Gen Diagn Pathol. 1997; 142(3-4):191-8. View

13.

Zhao C, Shen Y, Tao X, Xu J, Lu J, Liu C . Silencing of CtBP1 suppresses the migration in human glioma cells. J Mol Histol. 2016; 47(3):297-304. DOI: 10.1007/s10735-016-9678-z. View

14.

Connor J, Menzies S, St Martin S, Mufson E . Cellular distribution of transferrin, ferritin, and iron in normal and aged human brains. J Neurosci Res. 1990; 27(4):595-611. DOI: 10.1002/jnr.490270421. View

15.

Schwammle V, Leon I, Jensen O . Assessment and improvement of statistical tools for comparative proteomics analysis of sparse data sets with few experimental replicates. J Proteome Res. 2013; 12(9):3874-83. DOI: 10.1021/pr400045u. View

16.

Meng Q, Xing Y, Ren T, Lu H, Xi Y, Jiang Z . Mammalian Eps15 homology domain 1 promotes metastasis in non-small cell lung cancer by inducing epithelial-mesenchymal transition. Oncotarget. 2016; 8(14):22433-22442. PMC: 5410234. DOI: 10.18632/oncotarget.11220. View

17.

Vizcaino J, Cote R, Csordas A, Dianes J, Fabregat A, Foster J . The PRoteomics IDEntifications (PRIDE) database and associated tools: status in 2013. Nucleic Acids Res. 2012; 41(Database issue):D1063-9. PMC: 3531176. DOI: 10.1093/nar/gks1262. View

18.

Hemmati H, Nakano I, Lazareff J, Masterman-Smith M, Geschwind D, Bronner-Fraser M . Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci U S A. 2003; 100(25):15178-83. PMC: 299944. DOI: 10.1073/pnas.2036535100. View

19.

Flavahan W, Wu Q, Hitomi M, Rahim N, Kim Y, Sloan A . Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake. Nat Neurosci. 2013; 16(10):1373-82. PMC: 3930177. DOI: 10.1038/nn.3510. View

20.

Lively S, Schlichter L . The microglial activation state regulates migration and roles of matrix-dissolving enzymes for invasion. J Neuroinflammation. 2013; 10:75. PMC: 3693964. DOI: 10.1186/1742-2094-10-75. View