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  - 
TY  - CHAP
A1  - Motaln, Helena
A1  - Schuchhardt, Johannes
A1  - Stec, Karol
A1  - Breznik, Barbara
A1  - Ulrich, Henning
A1  - Lah, Tamara T.
T1  - Paradoxical role of mesenchymal stem cells in the glioblastoma  microenvironment
T2  - Anticancer research : international journal of cancer research and treatment
Y1  - 2014
SN  - 0250-7005
SN  - 1791-7530
VL  - 34
IS  - 10
SP  - 6071
EP  - 6072
PB  - International Institute of Anticancer Research
CY  - Athens
ER  - 
TY  - JOUR
A1  - Schichor, Christian
A1  - Albrecht, Valerie
A1  - Korte, Benjamin
A1  - Buchner, Alexander
A1  - Riesenberg, Rainer
A1  - Mysliwietz, Josef
A1  - Paron, Igor
A1  - Motaln, Helena
A1  - Turnsek, Tamara Lah
A1  - Juerchott, Kathrin
A1  - Selbig, Joachim
A1  - Tonn, Jörg-Christian
T1  - Mesenchymal stem cells and glioma cells form a structural as well as a functional syncytium in vitro
JF  - Experimental neurology
N2  - The interaction of human mesenchymal stem cells (hMSCs) and tumor cells has been investigated in various contexts. HMSCs are considered as cellular treatment vectors based on their capacity to migrate towards a malignant lesion. However, concerns about unpredictable behavior of transplanted hMSCs are accumulating. In malignant gliomas, the recruitment mechanism is driven by glioma-secreted factors which lead to accumulation of both, tissue specific stem cells as well as bone marrow derived hMSCs within the tumor. The aim of the present work was to study specific cellular interactions between hMSCs and glioma cells in vitro. We show, that glioma cells as well as hMSCs differentially express connexins. and that they interact via gap-junctional coupling. Besides this so-called functional syncytium formation, we also provide evidence of cell fusion events (structural syncytium). These complex cellular interactions led to an enhanced migration and altered proliferation of both, tumor and mesenchymal stem cell types in vitro. The presented work shows that glioma cells display signs of functional as well as structural syncytium formation with hMSCs in vitro. The described cellular phenomena provide new insight into the complexity of interaction patterns between tumor cells and host cells. Based on these findings, further studies are warranted to define the impact of a functional or structural syncytium formation on malignant tumors and cell based therapies in vivo.
KW  - Mesenchymal stem cell
KW  - Glioma
KW  - Syncytium
KW  - Gap junction
KW  - Fusion
Y1  - 2012
U6  - https://doi.org/10.1016/j.expneurol.2011.12.033
SN  - 0014-4886
VL  - 234
IS  - 1
SP  - 208
EP  - 219
PB  - Elsevier
CY  - San Diego
ER  -