gms | German Medical Science

63rd Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Japanese Neurosurgical Society (JNS)

German Society of Neurosurgery (DGNC)

13 - 16 June 2012, Leipzig

The zinc importer ZIP9 as mediator of glioma invasion

Meeting Abstract

  • S. Wernhart - Klinik für Neurochirurgie, Philipps-Universität Marburg
  • C. Hogstrand - Nutritional Sciences Division, King's College London, London, United Kingdom
  • J.W. Bartsch - Klinik für Neurochirurgie, Philipps-Universität Marburg
  • C. Nimsky - Klinik für Neurochirurgie, Philipps-Universität Marburg

Deutsche Gesellschaft für Neurochirurgie. Japanische Gesellschaft für Neurochirurgie. 63. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie (JNS). Leipzig, 13.-16.06.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. DocSA.01.01

doi: 10.3205/12dgnc299, urn:nbn:de:0183-12dgnc2998

Published: June 4, 2012

© 2012 Wernhart et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Objective: A hallmark of gliomas is their diffuse infiltration in surrounding CNS tissue. Zinc is an essential element for cell migration. Zinc utilisation is controlled by zinc transporters and through buffering by metallothioneins and glutathione. Thus, zinc could mediate invasiveness and metastatic potential of glioma cells. Since both zinc-treatment and zinc-chelation can have detrimental effects on tumor cells, we aimed to investigate the individual expression profiles of zinc importers (ZIPs) and transporters (ZnT) in 6 human glioma cell lines (U373, U251, G28, G112, A172, U87) and their vulnerability to TPEN (N,N,N',N'-tetrakis 2-pyridylmethyl ethylenediamine) induced zinc chelation.

Methods: Resilience of glioma cell lines to TPEN treatment was tested by MTT proliferation assays. Using sublethal doses of TPEN (≤1 μM), we analysed expression levels of ZnTs and ZIPs by qRT-PCR in the six glioma cell lines. In addition, migration behaviour of glioma cell lines was assessed by performing scratch assays. Those ZnTs and ZIPs that were induced by sublethal doses of TPEN were analysed further by overexpression and knockdown experiments and the effect on cell migration and on intracellular kinase activation was tested.

Results: Upon zinc depletion using 1 μM TPEN, we demonstrated that ZIP9 is selectively upregulated in expression levels in G28 and A172 glioma cells. In these cell lines, ZIP9 induction is correlated with cell migration and invasiveness. By analysis of intracellular signalling we demonstrated that ZIP9 is able to cause phophorylation of migration-relevant kinases such as Akt.

Conclusions: We have demonstrated that in particular ZIP9 is regulated by zinc depletion and that ZIP9 causes enhanced cell migration in glioma cells. Furthermore, ZIP9 acts on intracellular signalling as it causes phosphorylation of Akt, an important effector of cancer cell migration. Taken together, we defined particularly ZIP9 as an important mediator of cell migration in glioma cells.