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62. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgen (PNCH)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

07. - 11. Mai 2011, Hamburg

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Wnt-inhibitor DKK1 (Dickkopf 1) expression is determined by intercellular crosstalk and hypoxia in malignant gliomas

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  • corresponding author K.T. Guo - Tumor-biological Laboratory, Department of Neurosurgery, Ludwig-Maximilians-University, Campus Großhadern, Munich, Germany
  • P. Fu - Tumor-biological Laboratory, Department of Neurosurgery, Ludwig-Maximilians-University, Campus Großhadern, Munich, Germany
  • J.C. Tonn - Tumor-biological Laboratory, Department of Neurosurgery, Ludwig-Maximilians-University, Campus Großhadern, Munich, Germany
  • C. Schichor - Tumor-biological Laboratory, Department of Neurosurgery, Ludwig-Maximilians-University, Campus Großhadern, Munich, Germany

Deutsche Gesellschaft für Neurochirurgie. Polnische Gesellschaft für Neurochirurgen. 62. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgen (PNCH). Hamburg, 07.-11.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. DocP 028

doi: 10.3205/11dgnc249, urn:nbn:de:0183-11dgnc2492

Veröffentlicht: 28. April 2011

© 2011 Guo 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

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Objective: Wnt signalling pathways regulate proliferation, motility and survival in a variety of human cell types. DKK1 (Dickkopf 1) is a secreted Wnt inhibitory factor. It is described as tumor suppressor gene in breast cancer and a pro-apoptotic factor in glioma cells. In this study, we demonstrate the differentially regulated expression of DKK1 in human glioma cells, dependent on microenvironmental factors like hypoxia or on the intercellular crosstalk with bone marrow-derived stem cells.

Methods: 3 human gliomas cell lines (U373, U251 and U87), 5 cell lines from both human glioblastoma grade IV and human astrocytoma grade IV-derived mesenchymal stem cells, and 3 bone marrow-derived mesenchymal stem cell lines were selected for the experiment. The expression of DKK1 in cell lines under normoxia and hypoxia environment was measured using real time PCR and ELISA. The effect of DKK1 on cell migration and proliferation was observed by wound healing assays in vitro and SRB proliferation assays. DKK-1 expression under co-culture conditions of U87 glioma cells and bone marrow-derived mesenchymal stem cells under normoxia and hypoxia was detected by ELISA.

Results: Hypoxia led to an overexpression of DKK1 in malignant glioma cells compared to the normoxic environment. The wound healing assay showed an inhibitory effect of exogenous DKK1 on cell migration, reversed by an inhibitory antibody against DKK1. Exogenous DKK1 had no significant effects on cell proliferation. Co-culture of glioma cells with bone marrow-derived stem cells induced the expression of DKK1 in both cell lines.

Conclusions: In this study, we show a hypoxia dependency of DKK-1 expression in malignant glioma cell lines for the very first time. The induction of DKK1 by intracellular crosstalk or hypoxia sheds light on the intense adaption of glial tumor cells to environmental alterations.