gms | German Medical Science

58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

26. bis 29.04.2007, Leipzig

G-CSF and GM-CSF significantly increases the invasive phenotype of human primary glioma cells and cell lines in vitro

G-CSF und GM-CSF verstärkt den invasiven Phänotyp von humanen Glioblastom-Primärkulturen

Meeting Abstract

  • corresponding author G.H. Vince - Neurochirurgische Klinik der Julius-Maximilians Universität, Tumorbiologisches Labor, Würzburg
  • C. Hagemann - Neurochirurgische Klinik der Julius-Maximilians Universität, Tumorbiologisches Labor, Würzburg
  • P. Schuler - Neurochirurgische Klinik der Julius-Maximilians Universität, Tumorbiologisches Labor, Würzburg
  • E. Kunze - Neurochirurgische Klinik der Julius-Maximilians Universität, Tumorbiologisches Labor, Würzburg
  • C. Herbold - Neurochirurgische Klinik der Julius-Maximilians Universität, Tumorbiologisches Labor, Würzburg
  • K. Roosen - Neurochirurgische Klinik der Julius-Maximilians Universität, Tumorbiologisches Labor, Würzburg

Deutsche Gesellschaft für Neurochirurgie. 58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC). Leipzig, 26.-29.04.2007. Düsseldorf: German Medical Science GMS Publishing House; 2007. DocDO.02.08

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2007/07dgnc018.shtml

Veröffentlicht: 11. April 2007

© 2007 Vince 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 vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective: In cancer therapy GM-CSF is used to treat myelodepression and neutropenia. Recent data, however, is suggestive of a stimulating effect of GM-CSF on tumor cell proliferation. The present study investigates the influence of GM-CSF on the invasive potential of primary human glioblastoma cells and cell lines. Possible mechanisms for the observed effects are identified.

Methods: A total of 15 primary glioblastomas (taken from operative tumor samples, cultivated and centrifuged to pellets) and 3 glioma cell lines GaMG, U373 and D54 (tumor cell spheroids) were examined. The centrifuged pellets were examined. The tumor cells and spheroids were treated with 50, 100 and 150 ng/ml recombinant GM-CSF for 3 and 5 days. Adhesion, migration and confrontation assays were performed. Tumor cell viability was measured by MTT assay growth curves. Frozen sections were prepared and stained for collagenase A (MMP-2) and B (MMP-9), stromelysin-1 (MMP-3), matrilysin (MMP-7) and uPA. Semiquantitative RT-PCR and immunohistochemistry was performed for the collagenases and uPA. Additional routine HE and Ki-67 stains were performed.

Results: The treatment with GM-CSF at 100 ng/ml increased the amount of viable and proliferating tumor cells in all examined cell lines although the effect was slightly less pronounced in the primary cell cultures. No influence was seen with regard to adhesion for GaMG, U373 or D54. In the spheroid migration assay all GM-CSF stimulated cell lines displayed a pronounced increase in migration. Whereas upA, MMP-2 and MMP-9 mRNA was present in all examined cell lines, MMP-3 and MMP-7 mRNA became detectable after treatment only. Semiquantitative immunohistochemistry revealed a marked and dose-dependent increase of MMP-2, MMP-9 and uPA expression following treatment with GM-CSF in primary cells and cell lines.

Conclusions: GM-CSF stimulation of primary glioblastoma cells leads to a significant increase of cell migration and proliferation. Our data suggests that this effect may be the result of a dose-dependent increase in the proteolytic activity of tumor cells by an upregulation of serine and metalloproteases.