Abstract
Abstract The platelet derived growth factor (PDGF) signaling pathway is upregulated in many glioma subtypes, plays a role in gliomagenesis and promotes brain tumor progression. In this study, we demonstrate a role for PDGF signaling in the maintenance of brain tumor microenvironment homeostasis. We detected PDGFRa-expressing stromal cells potentially derived from oligodendritic precursor cells in both human and mouse high-grade gliomas. PDGFRa+ cells are predominately located at the invasive front of gliomas, and have a unique perivascular distribution. We suggest that these stromal cells play an important role in both initiating angiogenesis and supporting tumor progression. In an orthotopic model of glioma in PDGFRa deficient mice, tumor growth was significantly inhibited and gadolinium enhancement was decreased shown by bioluminescence and MRI, respectively. Glioma-associated blood vessels in PDGFRa knockout mice have smaller lumens and relatively normal vascular morphology. Glioma-associated oligodendritic precursor cells promoted endothelial sprouting and tubule formation by abrogating the inhibitory effect of astrocytes. We also demonstrated stromal-derived PDGF-CC as a key factor in the recruitment and activation of PDGFRa+ stromal cells. Utilizing PDGF-CC deficient mice, we recapitulate the glioma phenotype demonstrated in PDGFRa; knockout mice, suggesting their joint contribution to this pathway's integrity. In conclusion, the PDGF-CC/PDGFRa signaling axis in glioma stroma appears to contribute to the remodeling of the vascular architecture in the brain and influences subsequent angiogenesis. Citation Format: Yujie Huang, David Lyden, Jeffrey Greenfield. Oligodendritic precursor mediates vascular remodeling within glioma microenvironment in PDGF-C dependent manner. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B2.
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