This study was supported by grants from the Baxter Foundation (VT), Stanford MedScholar Program (JGS), and ECS Brain Tumor Research Fund (VT and YY). We thank B. Hoyte for and D. Schaal for preparing and editing the manuscript. Some of the results presented in this paper were presented at the annual meeting of the American Association of Neurological Surgeons 2004 (USA).
Incorporation of Naïve Bone Marrow Derived Cells into the Vascular Architecture of Brain Tumor
Version of Record online: 26 JAN 2010
Volume 11, Issue 8, pages 699–708, December 2004
How to Cite
YUNG, Y. C., CHESHIER, S., SANTARELLI, J. G., HUANG, Z., WAGERS, A., WEISSMAN, I. and TSE, V. (2004), Incorporation of Naïve Bone Marrow Derived Cells into the Vascular Architecture of Brain Tumor. Microcirculation, 11: 699–708. doi: 10.1080/10739680490521005
- Issue online: 26 JAN 2010
- Version of Record online: 26 JAN 2010
- Received 19 February 2004; accepted 6 August 2004.
- bone marrow cells;
- brain tumor;
- endothelial progenitor cells;
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.
Conclusion: 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.