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NG2 Proteoglycan‐Dependent Contributions of Pericytes and Macrophages to Brain Tumor Vascularization and Progression
Author(s) -
Stallcup William B.,
You WeonKyoo,
Kucharova Karolina,
CejudoMartin Pilar,
Yotsumoto Fusanori
Publication year - 2016
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/micc.12251
Subject(s) - extravasation , stromal cell , integrin , endothelium , cancer research , endothelial stem cell , angiogenesis , microbiology and biotechnology , biology , chemistry , immunology , cell , in vitro , endocrinology , biochemistry , genetics
The NG2 proteoglycan promotes tumor growth as a component of both tumor and stromal cells. Using intracranial, NG2‐negative B16F10 melanomas, we have investigated the importance of PC and Mac NG2 in brain tumor progression. Reduced melanoma growth in Mac‐NG2ko and PC‐NG2ko mice demonstrates the importance of NG2 in both stromal compartments. In each genotype, the loss of PC–endothelial cell interaction diminishes the formation of endothelial junctions and assembly of the basal lamina. Tumor vessels in Mac‐NG2ko mice have smaller diameters, reduced patency, and increased leakiness compared to PC‐NG2ko mice, thus decreasing tumor blood supply and increasing hypoxia. While the reduced PC interaction with endothelial cells in PC‐NG2ko mice results from the loss of PC activation of β 1 integrin signaling in endothelial cells, reduced PC–endothelial cell interaction in Mac‐NG2ko mice results from 90% reduced Mac recruitment. The absence of Mac‐derived signals in Mac‐NG2ko mice causes the loss of PC association with endothelial cells. Reduced Mac recruitment may be due to diminished activation of integrins in the absence of NG2, causing decreased Mac interaction with endothelial adhesion molecules that are needed for extravasation. These results reflect the complex interplay that occurs between Mac, PC, and endothelial cells during tumor vascularization.