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Supplementary Figure 4 from VEGF Regulates Region-Specific Localization of Perivascular Bone Marrow–Derived Cells in Glioblastoma

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posted on 2023-03-30, 22:30 authored by Kelly Burrell, Sanjay Singh, Shahrzad Jalali, Richard P. Hill, Gelareh Zadeh

PDF file - 1139KB, At early stages of tumor growth BMDCs exist in a differentiated state through the central and peripheral regions. At later stages the differentiated BMDCs are lost in the vasculature in the central regions but retained in the periphery (A). Following inhibition of VEGF through direct drug therapy, VEGFtrap (C), or indirectly, RTx (B), there is a compensatory up-regulation of ANG2, which in turn initiates the recruitment of differentiated BMDCs back to central vessels.

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ARTICLE ABSTRACT

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. Cancer Res; 74(14); 3727–39. ©2014 AACR.