TY  - JOUR
A1  - Guo, Ke-Tai
A1  - Fu, Peng
A1  - Juerchott, Kathrin
A1  - Motaln, Helena
A1  - Selbig, Joachim
A1  - Lah, Tamara T.
A1  - Tonn, Jörg-Christian
A1  - Schichor, Christian
T1  - The expression of Wnt-inhibitor DKK1 (Dickkopf 1) is determined by intercellular crosstalk and hypoxia in human malignant gliomas
JF  - Journal of cancer research and clinical oncology : official organ of the Deutsche Krebsgesellschaft
N2  - Objective Wnt signalling pathways regulate proliferation, motility and survival in a variety of human cell types. Dickkopf 1 (DKK1) gene codes for a secreted Wnt inhibitory factor. It functions as tumour suppressor gene in breast cancer and as a pro-apoptotic factor in glioma cells. In this study, we aimed to demonstrate whether the different expression of DKK1 in human glioma-derived cells is dependent on microenvironmental factors like hypoxia and regulated by the intercellular crosstalk with bone-marrow-derived mesenchymal stem cells (bmMSCs).
 Methods Glioma cell line U87-MG, three cell lines from human glioblastoma grade IV (glioma-derived mesenchymal stem cells) and three bmMSCs were selected for the experiment. The expression of DKK1 in cell lines under normoxic/hypoxic environment or co-culture condition was measured using real-time PCR and enzyme-linked immunoadsorbent assay. The effect of DKK1 on cell migration and proliferation was evaluated by in vitro wound healing assays and sulphorhodamine assays, respectively.
 Results Glioma-derived cells U87-MG displayed lower DKK1 expression compared with bmMSCs. Hypoxia led to an overexpression of DKK1 in bmMSCs and U87-MG when compared to normoxic environment, whereas co-culture of U87-MG with bmMSCs induced the expression of DKK1 in both cell lines. Exogenous recombinant DKK1 inhibited cell migration on all cell lines, but did not have a significant effect on cell proliferation of bmMSCs and glioma cell lines.
 Conclusion In this study, we showed for the first time that the expression of DKK1 was hypoxia dependent in human malignant glioma cell lines. The induction of DKK1 by intracellular crosstalk or hypoxia stimuli sheds light on the intense adaption of glial tumour cells to environmental alterations.
KW  - Dickkopf 1
KW  - Intercellular crosstalk
KW  - Hypoxia
KW  - Gliomas
Y1  - 2014
U6  - https://doi.org/10.1007/s00432-014-1642-2
SN  - 0171-5216
SN  - 1432-1335
VL  - 140
IS  - 8
SP  - 1261
EP  - 1270
PB  - Springer
CY  - New York
ER  -