Incorporation of naive bone marrow derived cells into the vascular architecture of brain tumor.
OBJECTIVE
Neovascularization is essential for tumor growth and invasion. Mounting evidence suggests that tumor cells recruit circulating endothelial progenitor cells to promote vasculogenesis to compliment tumor angiogenesis. This study examines the constitutive role of bone marrow-derived cells in this process.


METHODS
Rat glioma cells were implanted into brains of T-cell-depleted knockout mice. At various timepoints after tumor implantation, naïve bone marrow cells from ubiquitous transgenic mice expressing green fluorescent protein (GFP) were infused into these animals. The incorporation of GFP-positive cells into the vascular architecture was visualized by fluorescence confocal microscopy in conjunction with the transcription profiles of vascular endothelial growth factor (VEGF) and angiopoietin-1 and -2 (Ang-1 and Ang-2).


RESULTS
Of the cells infused, 8 days after tumor implantation, 0.49% were found exclusively sequestered in the vicinity of tumor vessels. This coincided with a decline in the expression of Ang-1 and a rise in the expression of VEGF and Ang-2. A few of these cells (0.66 of the 0.49%) localized onto the vascular wall. They resembled endothelial cells and expressed vWF.


CONCLUSIONS
The incorporation of bone marrow-derived unpurified endothelial cells into the tumor vascular bed is both time-limited and infrequent. These cells may play a supportive rather than a constitutive role in tumor neovascularization.
Yung
Yun C
YC
Department of Neurosurgery, Stanford University, California, USA.
Cheshier
Samuel
S
Santarelli
Justin G
JG
Huang
Zan
Z
Wagers
Amy
A
Weissman
Irving
I
Tse
Victor
V
D042501:Angiogenic Proteins / Q000235:genetics; D000818:Animals; D001808:Blood Vessels / Q000473:pathology*; D001854:Bone Marrow Cells / Q000378:metabolism / Q000502:physiology*; D001932:Brain Neoplasms / Q000098:blood supply*; D002465:Cell Movement / Q000502:physiology*; D042783:Endothelial Cells; D020869:Gene Expression Profiling; D005910:Glioma / Q000473:pathology; D049452:Green Fluorescent Proteins; D051379:Mice; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D014183:Transplantation, Heterologous
D042501:Angiogenic Proteins; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins