TY  - JOUR
A1  - Guo, Ke-Tai
A1  - Jürchott, Kathrin
A1  - Fu, Peng
A1  - Selbig, Joachim
A1  - Eigenbrod, Sabina
A1  - Tonn, Jörg-Christian
A1  - Schichor, Christian
T1  - Isolation and characterization of bone marrow-derived progenitor cells from malignant gliomas
JF  - Anticancer research : international journal of cancer research and treatment
N2  - Background: Malignant gliomas are highly-vascularised tumours. Neoangiogenesis is a crucial factor in the malignant behaviour of tumour and prognosis of patients. Several mechanisms are suspected to lead to neoangiogenesis, one of them is the recruitment of multipotent progenitor cells towards the tumour. Factors such as Vascular endothelial growth factor-A (VEGF-A) were described to recruit bone marrow-derived endothelial progenitor cells (EPCs) to the glioma stroma and vasculature. Little is known about isolating EPCs from normal or malignant tissues. Materials and Methods: In this study, we addressed the topic of characterization of tumour-isolated EPCs and re-defined the clonal relationship between EPCs and hematopoietic stem cells (HSCs) in gliomas. We first checked public gene expression data of glioma for putative marker expression, pointing towards a prevalence of EPCs and HSCs in glioma. Immunohistochemical staining of glioma tissue confirmed the higher expression of these progenitor markers in glioma tissue. EPCs and HSCs were consequently isolated and characterized at the phenotypic and functional levels. We applied a new isolation method, for the first time, to specimen from patients with high grade glioma including seven grade IV glioblastoma, five-grade III astrocytoma, and three grade III oligoastrocytoma. Results: In all samples, we were able to isolate the tumour-derived EPCs, which were positive for characteristic markers: CD31, CD34 and VEGFR2. The EPCs formed capillary networks in vitro and had the ability to take up acetylated low-density lipoprotein. Glioma-derived HSCs were positive for CD34 and CD45, but they were unable to form a capillary network in vitro. These findings on tumour-derived EPCs/HSCs were in concordance with the results, derived from peripheral blood of healthy volunteers. Conclusion: In our study, we established a new method for EPC/HSC isolation from human gliomas, defined the contribution of EPCs and HSCs to the tumour tissue, and highlighted the intense in vivo tumour host interaction.
KW  - Glioma
KW  - endothelial progenitor cell
KW  - hematopoietic stem cell
Y1  - 2012
SN  - 0250-7005
VL  - 32
IS  - 11
SP  - 4971
EP  - 4982
PB  - International Institute of Anticancer Research
CY  - Athens
ER  - 
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  -