TY - JOUR
T1 - VEGF regulates region-specific localization of perivascular bone marrow-derived cells in glioblastoma
AU - Burrell, Kelly
AU - Singh, Sanjay
AU - Jalali, Shahrzad
AU - Hill, Richard P.
AU - Zadeh, Gelareh
PY - 2014/7/15
Y1 - 2014/7/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84904257642&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84904257642&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-13-3119
DO - 10.1158/0008-5472.CAN-13-3119
M3 - Article
C2 - 24820020
AN - SCOPUS:84904257642
SN - 0008-5472
VL - 74
SP - 3727
EP - 3739
JO - Cancer Research
JF - Cancer Research
IS - 14
ER -