Article
Distinct bone marrow derived populations contribute to angiogenesis in malignant gliomas
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Authors
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Ke-Tai Guo
- Tumor-biological Laboratory, Department of Neurosurgery, Ludwig-Maximilians-University, Munich, Campus Großhadern, Germany
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Kathrin Juerchott
- Institute of Biology and biochemistry, Department of bioinformatics, University of Potsdam, Postdam, Germany
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Peng Fu
- Tumor-biological Laboratory, Department of Neurosurgery, Ludwig-Maximilians-University, Munich, Campus Großhadern, Germany
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Jörg-Christian Tonn
- Tumor-biological Laboratory, Department of Neurosurgery, Ludwig-Maximilians-University, Munich, Campus Großhadern, Germany
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Joachim Selbig
- Institute of Biology and biochemistry, Department of bioinformatics, University of Potsdam, Postdam, Germany
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Christian Schichor
- Tumor-biological Laboratory, Department of Neurosurgery, Ludwig-Maximilians-University, Munich, Campus Großhadern, Germany
| Published: | September 16, 2010 |
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Outline
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Objective: Malignant gliomas are highly vascularised tumors. Production of attracting factors like VEGF (Vascular Endothelial Growth Factor) leads to a recruitment of endothelial progenitor cells (EPCs) to the tumor stroma and vasculature. Recently two types of circulating progenitor cells have been identified in the peripheral blood of healthy volunteers: Endothelial colony forming cells (ECFCs) and colony forming unit-endothelial cells (CFU-ECs) (Yoder et al, 2007). The CFU-ECs were identified to be derived from hematopoietic system (HPCs-derived cells); the ECFCs showed the ability to form colonies and were identified as endothelial progenitor cells (EPCs).
Methods: Assuming that secreted recruitment factors lead to accumulation of these circulating cells in tumor tissue, we analyzed microarray whole genome expression data, where we found differential expression of EPC as well as HPC markers. By establishing the isolation method on tumor tissue, we investigated cells, derived from high grade gliomas including 7 glioblastoma grade IV, 4 astrocytoma grade III, 4 Oligoastrocytoma grade III.
Results: All of the tumor-derived EPCs showed the typical endothelial phenotypes (CD31+, CD105+, UEA-1+); on a functional level, they could form capillary networks in vitro and had the ability to uptake AcLDL. The HPC-derived cells showed typical hematopoietic markers like CD34 and CD45, but were unable to form a capillary network in vitro. The immunohistochemistry staining of tumor tissue confirmed the prevalence of these cells in glioma tissue as well as their contribution to the tumor vessels.
Conclusions: This rapid and effective isolation method greatly facilitates the isolation and propagation of human malignant glioma-derived progenitor cells. For the first time, we describe different bone marrow derived cell types, contributing to angiogenesis in malignant gliomas.
