gms | German Medical Science

68th Annual Meeting of the German Society of Neurosurgery (DGNC)
7th Joint Meeting with the British Neurosurgical Society (SBNS)

German Society of Neurosurgery (DGNC)

14 - 17 May 2017, Magdeburg

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Silencing of the nucleocytoplasmic carriers Karyopherin a2 suppresses gliomagenesis in the U-87MG glioblastoma cell line

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  • Konstantinos Gousias - Abteilung für BG Neurochirurgie und Neurotraumatologie, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Bochum, Deutschland
  • Angeliki Datsi - Bochum, Deutschland
  • Maren Stallkamp - Bochum, Deutschland
  • Bogdan Pintea - Bochum, Deutschland
  • Ramon Martinez - Bochum, Deutschland

Deutsche Gesellschaft für Neurochirurgie. Society of British Neurological Surgeons. 68. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 7. Joint Meeting mit der Society of British Neurological Surgeons (SBNS). Magdeburg, 14.-17.05.2017. Düsseldorf: German Medical Science GMS Publishing House; 2017. DocMi.03.02

doi: 10.3205/17dgnc372, urn:nbn:de:0183-17dgnc3722

Published: June 9, 2017

© 2017 Gousias et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

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Objective: We have previously shown that karyopherin a2 (KPNA2), an important nucleocytoplasmic shuttling receptor, is overexpressed in malignant diffuse astrocytomas and, moreover its expression is inversely associated with patient prognosis. However, the pathophysiological contribution of KPNA2 to gliomagenesis is still partially devised. Our study aims for the first time to further elucidate the promoting role of KPNA2 in the pathogenesis of glioblastoma by means of analysing a variety of human glioblastoma cell lines.

Methods: Cell culture analysis has been conducted on U-87MG, U-373MG, U-138MG and U-118MG commercial human glioblastoma cell lines. Nuclear and cytoplasmic expression of KPNA2 has been evaluated quantitatively via flow cytometry (BD FACS Canto). Silencing of KPNA2 has been conducted by small interfering RNA (siRNA). The proliferative capacity of the cells has been determined via flow cytometry. KPNA2wild type vs. KPNA2knock down glioblastoma cells have been compared in terms of proliferation capacity, cell cycle function as well as subcellular localisation of known transcription factors, such as Oct4, NF-kB and c-Myc. Statistical analysis used standard procedures.

Results: U-87MG glioblastoma cell lines showed higher proliferation, less adherence, outgrowth in 3D clusters as well as higher expression of KPNA2, all of them conferring higher malignant behaviour, in comparison to the remaining cell lines. Silencing of KPNA2 in those cells highly expressing KPNA2 significantly decreased its proliferative capacity (p<0.05). Further, siRNA interference of KPNA2 resulted in G1 cell cycle phase arrest in the U-87MG cell line in the first 48 hours (p<0.05). KPNA2 silencing led to increased subcellular translocation of all above mentioned transcription factors.

Conclusion: This study confirms also in in vitro glioblastoma models that a high expression of KPNA2 is associated with a more malignant phenotype. While increased expression of KPNA2 in human glioblastoma cells promotes proliferation, invasion and aggressiveness of the tumorigenic cell pattern, silencing of KPNA2 was associated with a less malignant profile of U-87MG cells. Our results strongly suggest that silencing of KPNA2 may play an important role in modulation of the most malignant features of GBM cells.