Malignant gliomas actively recruit bone marrow stromal cells by secreting angiogenic cytokines.
The transplantation of progenitor cells is a promising new approach for the treatment of gliomas. Marrow stromal cells (MSC) are possible candidates for such a cell-based therapy, since they are readily and autologously available and show an extensive tropism to gliomas in vitro and in vivo. However, the signals that guide the MSC are still poorly understood. In this study, we show that gliomas have the capacity to actively attract MSC by secreting a multitude of angiogenic cytokines. We demonstrate that interleukin-8 (IL-8), transforming growth factor-ss1 (TGF-ss1) and neurotrophin-3 (NT-3) contribute to this glioma-directed tropism of human MSC. Together with the finding that vascular endothelial growth factor (VEGF) is another MSC-attracting factor secreted by glioma cells, these data support the hypothesis that gliomas use their angiogenic pathways to recruit mesenchymal progenitor cells.
Birnbaum
Tobias
T
Department of Neurology, Ludwig-Maximilians-University, Klinikum Grosshadern, Marchioninistr. 15, 81377 Munich, Germany. tobias.birnbaum@med.uni-muenchen.de
Roider
Julia
J
Schankin
Christoph J
CJ
Padovan
Claudio S
CS
Schichor
Christian
C
Goldbrunner
Roland
R
Straube
Andreas
A
D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D002633:Chemotaxis; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D020933:Neurotrophin 3 / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology; D015291:Transforming Growth Factors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D017077:Culture Media, Conditioned; D016207:Cytokines; D016209:Interleukin-8; D020933:Neurotrophin 3; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D015291:Transforming Growth Factors