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Cancers 2017, 9(4), 31; doi:10.3390/cancers9040031

NG2 Proteoglycan Enhances Brain Tumor Progression by Promoting Beta-1 Integrin Activation in both Cis and Trans Orientations

Sanford Burnham Prebys Medical Discovery Institute, Cancer Center, Tumor Microenvironment and Cancer Immunology Program, 10901 North Torrey Pines Road, La Jolla, CA 92037
Received: 28 February 2017 / Revised: 23 March 2017 / Accepted: 29 March 2017 / Published: 31 March 2017
(This article belongs to the Special Issue Integrins in Cancer)
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Abstract

By physically interacting with beta-1 integrins, the NG2 proteoglycan enhances activation of the integrin heterodimers. In glioma cells, co-localization of NG2 and 31 integrin in individual cells (cis interaction) can be demonstrated by immunolabeling, and the NG2-integrin interaction can be confirmed by co-immunoprecipitation. NG2-dependent integrin activation is detected via use of conformationally sensitive monoclonal antibodies that reveal the activated state of the beta-1 subunit in NG2-positive versus NG2-negative cells. NG2-dependent activation of beta-1 integrins triggers downstream activation of FAK and PI3K/Akt signaling, resulting in increased glioma cell proliferation, motility, and survival. Similar NG2-dependent cis activation of beta-1 integrins occurs in microvascular pericytes, leading to enhanced proliferation and motility of these vascular cells. Surprisingly, pericyte NG2 is also able to promote beta-1 integrin activation in closely apposed endothelial cells (trans interaction). Enhanced beta-1 signaling in endothelial cells promotes endothelial maturation by inducing the formation of endothelial junctions, resulting in increased barrier function of the endothelium and increased basal lamina assembly. NG2-dependent beta-1 integrin signaling is therefore important for tumor progression by virtue of its affects not only on the tumor cells themselves, but also on the maturation and function of tumor blood vessels. View Full-Text
Keywords: brain tumor progression; brain tumor vascularization; NG2 proteoglycan; beta-1 integrin; pericyte; endothelial cell; macrophage; tumor vessel function; Cre-Lox gene ablation brain tumor progression; brain tumor vascularization; NG2 proteoglycan; beta-1 integrin; pericyte; endothelial cell; macrophage; tumor vessel function; Cre-Lox gene ablation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Stallcup, W.B. NG2 Proteoglycan Enhances Brain Tumor Progression by Promoting Beta-1 Integrin Activation in both Cis and Trans Orientations. Cancers 2017, 9, 31.

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