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Publication : VEGF regulates region-specific localization of perivascular bone marrow-derived cells in glioblastoma.

First Author  Burrell K Year  2014
Journal  Cancer Res Volume  74
Issue  14 Pages  3727-39
PubMed ID  24820020 Mgi Jnum  J:212750
Mgi Id  MGI:5582116 Doi  10.1158/0008-5472.CAN-13-3119
Citation  Burrell K, et al. (2014) VEGF regulates region-specific localization of perivascular bone marrow-derived cells in glioblastoma. Cancer Res 74(14):3727-39
abstractText  Glioblastoma multiforme (GBM) is characterized by a pathogenic vasculature that drives aggressive local invasion. Recent work suggests that GBM cells recruit bone marrow-derived progenitor cells (BMDC) to facilitate recurrence after radiotherapy, but how this may be achieved is unclear. In this study, we established the spatiotemporal and regional contributions of perivascular BMDCs (pBMDC) to GBM development. We found an increased recruitment of BMDCs to GBM in response to tumor growth and following radiotherapy. However, in this study, BMDCs did not differentiate into endothelial cells directly but rather provided a perivascular support role. The pBMDCs were shown to associate with tumor vasculature in a highly region-dependent manner, with central vasculature requiring minimal pBMDC support. Region-dependent association of pBMDC was regulated by VEGF. In the absence of VEGF, following radiotherapy or antiangiogenic therapy, we documented an increase in Ang2 that regulated recruitment of pBMDCs to maintain the vulnerable central vasculature. Together, our results strongly suggested that targeting pBMDC influx along with radiation or antiangiogenic therapy would be critical to prevent vascular recurrence of GBM.
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