Vascular endothelial growth factor A contributes to glioma-induced migration of human marrow stromal cells (hMSC).
OBJECTIVE
It has been demonstrated that murine neural stem cells (mNSCs) and human mesenchymal stroma cells migrate toward experimental gliomas, making stem cells a candidate for cellular carrier systems of anti-glioma therapy. However, few data are available on the factors involved in regulating stem cell migration. The aim of our study was to characterize the migratory and invasive behavior of adult human marrow stromal cells (hMSC) that interact with glioma cells, especially focusing on vascular endothelial growth factor A (VEGF-A)-mediated effects.


METHODS
Human MSC were isolated from bone marrow biopsies carried out for hematological indications. The chemokinetic activity of hMSC in response to glioma-conditioned medium as well as VEGF-A was analyzed using a modified Boyden chamber assay. Invasion of hMSC and glioma spheroids was investigated using confrontational cultures. To provide analogous data from a well-described system, invasion of murine C17.2 neural stem cells was assessed. VEGF-A secretion by gliomas and the expression of VEGF-receptor 2 in hMSC were evaluated.


RESULTS
Human MSC showed an extensive invasion into glioma spheroids. Glioma-conditioned medium significantly increased hMSC migration and also invasion, driven by chemotaxis. VEGF-A also showed significant pro-migratory and pro-invasive effects on hMSC, but in a reduced fashion compared to glioma-conditioned medium.


CONCLUSIONS
Human MSC show intensive migratory and invasive behavior in the presence of glioma cells and glioma-conditioned medium. Among others, VEGF-A seems to be one important factor in enhancing and directing stem cell motility.
Department of Neurosurgery, Ludwig-Maximilians-University, Klinikum Grosshadern, Marchioninistr. 15, 81377 Munich, Germany. Christian.Schichor@med.uni-muenchen.de
Christian
C
Schichor
Tobias
T
Birnbaum
Nima
N
Etminan
Oliver
O
Schnell
Stefan
S
Grau
Sabine
S
Miebach
Karen
K
Aboody
Claudio
C
Padovan
Andreas
A
Straube
Jörg-Christian
JC
Tonn
Roland
R
Goldbrunner
D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005434:Flow Cytometry / Q000379:methods; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D005910:Glioma / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D018874:Spheroids, Cellular; D013997:Time Factors; D014162:Transfection / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology / Q000502:physiology*
D018925:Chemokines; D017077:Culture Media, Conditioned; D042461:Vascular Endothelial Growth Factor A; D049452:Green Fluorescent Proteins