The invasive proteome of glioblastoma revealed by laser-capture microdissection

Thomas Daubon; Joris Guyon; Anne-Aurélie Raymond; Benjamin Dartigues; Justine Rudewicz; Zakaria Ezzoukhry; Jean-William Dupuy; John M J Herbert; Frédéric Saltel; Rolf Bjerkvig; Macha Nikolski; Andreas Bikfalvi

doi:10.1093/noajnl/vdz029

The invasive proteome of glioblastoma revealed by laser-capture microdissection

Neurooncol Adv. 2019 Sep 28;1(1):vdz029. doi: 10.1093/noajnl/vdz029. eCollection 2019 May-Dec.

Authors

Thomas Daubon^{1

2

3}, Joris Guyon^{1

2}, Anne-Aurélie Raymond⁴, Benjamin Dartigues⁵, Justine Rudewicz^{1

2

5}, Zakaria Ezzoukhry⁴, Jean-William Dupuy⁶, John M J Herbert⁷, Frédéric Saltel^{8

4}, Rolf Bjerkvig^{3

9

10}, Macha Nikolski^{5

11}, Andreas Bikfalvi^{1

2}

Affiliations

¹ INSERM U1029, Pessac, France.
² LAMC, University of Bordeaux, Bordeaux, France.
³ KG Jebsen Brain Tumour Research Center, University of Bergen, Bergen, Norway.
⁴ Oncoprot, TBM Core US005 University of Bordeaux, France.
⁵ Bordeaux Bioinformatics Center, CBiB University of Bordeaux, France.
⁶ Plateforme Protéome, University of Bordeaux, Bordeaux, France.
⁷ Disease Gene Discovery Limited, London, UK.
⁸ University Bordeaux, INSERM UMR1053, BaRITOn Bordeaux Research in Translational Oncology, Bordeaux, France.
⁹ NorLux Neuro-Oncology, Department of Biomedicine University of Bergen, Norway.
¹⁰ Oncology Department, Luxembourg Institute of Health 84, Val Fleuri, Luxembourg.
¹¹ LaBRI, UMR5800 University of Bordeaux, Talence, France.

Abstract

Background: Glioblastomas are heterogeneous tumors composed of a necrotic and tumor core and an invasive periphery.

Methods: Here, we performed a proteomics analysis of laser-capture micro-dissected glioblastoma core and invasive areas of patient-derived xenografts.

Results: Bioinformatics analysis identified enriched proteins in central and invasive tumor areas. Novel markers of invasion were identified, the genes proteolipid protein 1 (PLP1) and Dynamin-1 (DNM1), which were subsequently validated in tumors and by functional assays.

Conclusions: In summary, our results identify new networks and molecules that may play an important role in glioblastoma development and may constitute potential novel therapeutic targets.

Keywords: glioblastoma; intratumor heterogeneity; invasion; patient-derived xenograft; proteomics analysis.