gms | German Medical Science

65. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

11. - 14. Mai 2014, Dresden

MACC1 regulates migration and invasion of glioblastoma cells

Meeting Abstract

  • Carsten Hagemann - Universitätsklinikum Würzburg, Neurochirurgische Klinik und Poliklinik, Tumorbiologisches Labor, Würzburg
  • Steffen Fuchs - Universitätsklinikum Würzburg, Neurochirurgische Klinik und Poliklinik, Tumorbiologisches Labor, Würzburg
  • Almuth F. Kessler - Universitätsklinikum Würzburg, Neurochirurgische Klinik und Poliklinik, Tumorbiologisches Labor, Würzburg
  • Pia Herrmann - Experimental and Clinical Research Center, Charité – Universitätsmedizin Berlin, Max-Delbrück-Zentrum für Molekulare Medizin, Berlin
  • Janice Smith - Experimental and Clinical Research Center, Charité – Universitätsmedizin Berlin, Max-Delbrück-Zentrum für Molekulare Medizin, Berlin
  • Tim Hohmann - Martin-Luther-Universität Halle-Wittenberg, Institut für Anatomie und Zellbiologie, Halle/Saale
  • Urszula Grabiec - Martin-Luther-Universität Halle-Wittenberg, Institut für Anatomie und Zellbiologie, Halle/Saale
  • Thomas Linsenmann - Universitätsklinikum Würzburg, Neurochirurgische Klinik und Poliklinik, Tumorbiologisches Labor, Würzburg
  • Faramarz Dehghani - Martin-Luther-Universität Halle-Wittenberg, Institut für Anatomie und Zellbiologie, Halle/Saale
  • Ralf-Ingo Ernestus - Universitätsklinikum Würzburg, Neurochirurgische Klinik und Poliklinik, Tumorbiologisches Labor, Würzburg
  • Mario Löhr - Universitätsklinikum Würzburg, Neurochirurgische Klinik und Poliklinik, Tumorbiologisches Labor, Würzburg
  • Ulrike Stein - Experimental and Clinical Research Center, Charité – Universitätsmedizin Berlin, Max-Delbrück-Zentrum für Molekulare Medizin, Berlin

Deutsche Gesellschaft für Neurochirurgie. 65. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC). Dresden, 11.-14.05.2014. Düsseldorf: German Medical Science GMS Publishing House; 2014. DocMI.15.03

doi: 10.3205/14dgnc353, urn:nbn:de:0183-14dgnc3537

Veröffentlicht: 13. Mai 2014

© 2014 Hagemann et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective: Metastasis-associated in colon cancer-1 (MACC1) has been established as an independent prognostic indicator of metastasis formation and metastasis-free survival for colon carcinomas. Although Glioblastoma multiforme (GBM) rarely metastasize, their invasive and migratory behavior is similar to those of metastatic cells of tumors with different origin. Recently, we presented data indicating that MACC1 expression levels were associated with the WHO grading of gliomas on mRNA- and protein-level. MACC1 expression allowed discrimination of dormant and recurrent LGA and of primary and secondary GBM. Finally, transient MACC1 overexpression promoted proliferation and migration of GBM cells.

Method: Data mining of publicly available databases was performed to confirm overexpression of MACC1 based on Oncomine microarray and The Cancer Genome Atlas (TCGA) data. Migration of primary GBM cell cultures from patients' was evaluated by spheroid-migration assays. The MACC1-transfected GBM cell line U138 was used for real-time measurements (xCELLigence) of migration and invasion in conjunction with the Met inhibitor crizotinib. Tumor formation capabilities were evaluated in organotypic hippocampal slice cultures (OHSC) of mice.

Results: MACC1 overexpression by GBM was confirmed on large sample sets. Its overexpression correlated with amplification of chromosome 7. Endogenous expression of MACC1 was variable in primary cells derived from GBM tumors. However, its expression level positively correlated with migration of these cells in a spheroid assay. In OHSC MACC1 increased the migratory, invasive and tumor formation abilities of GBM cells, whereas the Met inhibitor crizotinib caused a reversion back to basal level. MACC1 overexpression triggered an increase of Met expression. This could be a first indication, that MACC1 effects in GBM could be procured via regulation of Met expression.

Conclusions: MACC1 influences migration and invasion of GBM cells potentially by regulation of the hepatocyte growth factor (HGF) receptor Met. Inhibition of MACC1 may be a new therapeutic strategy for the inhibition of GBM cell migration and invasion.