@article{TimmerTheissJuerchottetal.2010,
  author    = {Timmer, Marco and Theiss, Hans and J{\"u}rchott, Katrin and Ries, Christian and Paron, Igor and Franz, W. and Selbig, Joachim and Guo, Ketai and Tonn, J{\"o}rg and Schichor, Christian},
  title     = {Stromal-Derived Factor 1a (Sdf-1a), a Homing Factor for Mesenchymal Progenitor Cells, Is Elevated in Tumor Tissue and Plasma of Glioma Patients},
  issn      = {1522-8517},
  year      = {2010},
  abstract  = {Malignant gliomas are a fatal disease lacking sufficient possibilities for early diagnosis and chemical markers to detect remission or relapse. The recruitment of progenitor cells such as mesenchymal stem cells (MSC) is a main feature of gliomas. Stromal cell-derived factor-1 (SDF-1), a chemokine produced in glioma cell lines, enhances migration in MSC and has been associated with cell survival and apoptosis in gliomas. Therefore, this study was performed to evaluate (i) whether SDF-1 and its receptors are expressed in human malignant gliomas in situ and (ii) if SDF-1 might potentially play a role in recruiting MSCs into human glioma. In glioblastoma tissue, immunohistochemistry revealed that SDF-1 and its receptor CXCR4 are expressed in regions of angiogenesis and necrosis, and qPCR showed that SDF-1 is elevated. Public expression data indicated that CXCR4 was upregulated. The latter data also illustrate that SDF-1 could be up- or downregulated in glioma compared to normal brain in a transcript-specific manner. In plasma, SDF-1 is elevated in glioma patients. The level is reduced by both dexamethasone intake and surgery. Dexamethasone also decreased SDF-1 production in cells in vitro. The undirected migration of human MSC (hMSC) was not enhanced by the addition of SDF-1. However, SDF-1 stimulated directed invasion of hMSC in a dose-dependent manner. Taken together, we show that SDF-1 is a potent chemoattractant of progenitor cells such as hMSCs and that its expression is elevated in glioma tissue, which results in elevated SDF-1 levels in the patient's plasma samples with concomittant decrease after tumor resection. The fact that elevated SDF-1 plasma levels are significantly decreased after tumor surgery could be a first hint that SDF-1 might act as tumor marker for malignant gliomas in order to detect disease progression or remission, respectively.},
  language  = {en}
}
@article{JuerchottGuoCatchpoleetal.2011,
  author    = {Juerchott, Kathrin and Guo, Ke-Tai and Catchpole, Gareth and Feher, Kristen and Willmitzer, Lothar and Schichor, Christian and Selbig, Joachim},
  title     = {Comparison of metabolite profiles in U87 glioma cells and mesenchymal stem cells},
  series = {Biosystems : journal of biological and information processing sciences},
  volume    = {105},
  journal   = {Biosystems : journal of biological and information processing sciences},
  number    = {2},
  publisher = {Elsevier},
  address   = {Oxford},
  issn      = {0303-2647},
  doi       = {10.1016/j.biosystems.2011.05.005},
  pages     = {130 -- 139},
  year      = {2011},
  abstract  = {Gas chromatography-mass spectrometry (GC-MS) profiles were generated from U87 glioma cells and human mesenchymal stem cells (hMSC). 37 metabolites representing glycolysis intermediates, TCA cycle metabolites, amino acids and lipids were selected for a detailed analysis. The concentrations of these. metabolites were compared and Pearson correlation coefficients were used to calculate the relationship between pairs of metabolites. Metabolite profiles and correlation patterns differ significantly between the two cell lines. These profiles can be considered as a signature of the underlying biochemical system and provide snap-shots of the metabolism in mesenchymal stem cells and tumor cells.},
  language  = {en}
}
@article{SchichorAlbrechtKorteetal.2012,
  author    = {Schichor, Christian and Albrecht, Valerie and Korte, Benjamin and Buchner, Alexander and Riesenberg, Rainer and Mysliwietz, Josef and Paron, Igor and Motaln, Helena and Turnsek, Tamara Lah and Juerchott, Kathrin and Selbig, Joachim and Tonn, J{\"o}rg-Christian},
  title     = {Mesenchymal stem cells and glioma cells form a structural as well as a functional syncytium in vitro},
  series = {Experimental neurology},
  volume    = {234},
  journal   = {Experimental neurology},
  number    = {1},
  publisher = {Elsevier},
  address   = {San Diego},
  issn      = {0014-4886},
  doi       = {10.1016/j.expneurol.2011.12.033},
  pages     = {208 -- 219},
  year      = {2012},
  abstract  = {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.},
  language  = {en}
}
@article{GuoJuerchottFuetal.2012,
  author    = {Guo, Ke-Tai and J{\"u}rchott, Kathrin and Fu, Peng and Selbig, Joachim and Eigenbrod, Sabina and Tonn, J{\"o}rg-Christian and Schichor, Christian},
  title     = {Isolation and characterization of bone marrow-derived progenitor cells from malignant gliomas},
  series = {Anticancer research : international journal of cancer research and treatment},
  volume    = {32},
  journal   = {Anticancer research : international journal of cancer research and treatment},
  number    = {11},
  publisher = {International Institute of Anticancer Research},
  address   = {Athens},
  issn      = {0250-7005},
  pages     = {4971 -- 4982},
  year      = {2012},
  abstract  = {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.},
  language  = {en}
}
@article{GuoFuJuerchottetal.2014,
  author    = {Guo, Ke-Tai and Fu, Peng and Juerchott, Kathrin and Motaln, Helena and Selbig, Joachim and Lah, Tamara T. and Tonn, J{\"o}rg-Christian and Schichor, Christian},
  title     = {The expression of Wnt-inhibitor DKK1 (Dickkopf 1) is determined by intercellular crosstalk and hypoxia in human malignant gliomas},
  series = {Journal of cancer research and clinical oncology : official organ of the Deutsche Krebsgesellschaft},
  volume    = {140},
  journal   = {Journal of cancer research and clinical oncology : official organ of the Deutsche Krebsgesellschaft},
  number    = {8},
  publisher = {Springer},
  address   = {New York},
  issn      = {0171-5216},
  doi       = {10.1007/s00432-014-1642-2},
  pages     = {1261 -- 1270},
  year      = {2014},
  abstract  = {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.},
  language  = {en}
}
@article{BordagKlieJuerchottetal.2015,
  author    = {Bordag, Natalie and Klie, Sebastian and J{\"u}rchott, Kathrin and Vierheller, Janine and Schiewe, Hajo and Albrecht, Valerie and Tonn, J{\"o}rg-Christian and Schwartz, Christoph and Schichor, Christian and Selbig, Joachim},
  title     = {Glucocorticoid (dexamethasone)-induced metabolome changes in healthy males suggest prediction of response and side effects},
  series = {Scientific reports},
  volume    = {5},
  journal   = {Scientific reports},
  publisher = {Nature Publ. Group},
  address   = {London},
  issn      = {2045-2322},
  doi       = {10.1038/srep15954},
  pages     = {12},
  year      = {2015},
  abstract  = {Glucocorticoids are indispensable anti-inflammatory and decongestant drugs with high prevalence of use at (similar to)0.9\% of the adult population. Better holistic insights into glucocorticoid-induced changes are crucial for effective use as concurrent medication and management of adverse effects. The profiles of 214 metabolites from plasma of 20 male healthy volunteers were recorded prior to and after ingestion of a single dose of 4 mg dexamethasone (+20 mg pantoprazole). Samples were drawn at three predefined time points per day: seven untreated (day 1 midday - day 3 midday) and four treated (day 3 evening - day 4 evening) per volunteer. Statistical analysis revealed tremendous impact of dexamethasone on the metabolome with 150 of 214 metabolites being significantly deregulated on at least one time point after treatment (ANOVA, Benjamini-Hochberg corrected, q < 0.05). Inter-person variability was high and remained uninfluenced by treatment. The clearly visible circadian rhythm prior to treatment was almost completely suppressed and deregulated by dexamethasone. The results draw a holistic picture of the severe metabolic deregulation induced by single-dose, short-term glucocorticoid application. The observed metabolic changes suggest a potential for early detection of severe side effects, raising hope for personalized early countermeasures increasing quality of life and reducing health care costs.},
  language  = {en}
}