The glial precursor proteoglycan, NG2, is expressed on tumour neovasculature by vascular pericytes in human malignant brain tumours

Chekenya, Martha; Enger, Per Øyvind; Thorsen, Frits; Tysnes, Berit Bølge; Al‐Sarraj, Safa; Read, Tracy Ann; Furmanek, Tomasz; Mahesparan, Rupavathana; Levine, Joel M.; Butt, Arthur M.; Pilkington, G. J.; Bjerkvig, Rolf

doi:10.1046/j.1365-2990.2002.00412.x

Cited by 69 publications

(60 citation statements)

References 59 publications

(76 reference statements)

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“…3,71,[78][79][80] In the case of NG2, several reports suggest that expression of the proteoglycan is correlated with the degree of malignancy of the glioma. 72,73,[81][82][83][84] This would be consistent with our ideas concerning the ability NG2 to potentiate cell motility and cell proliferation in response to stimulation by growth factors and extracellular matrix components. This will be discussed more fully in a later section.…”

Section: Ng2 Expression In Gliomassupporting

confidence: 88%

A role for the NG2 proteoglycan in glioma progression

Stallcup

Huang

2008

Cell Adhesion & Migration

123

138

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Many human gliomas carry markers characteristic of oligodendrocyte progenitor cells (such as Olig-2, PDGF alpha receptor and NG2 proteoglycan), suggesting these progenitors as the cells of origin for glioma initiation. This review considers the potential roles of the NG2 proteoglycan in glioma progression. NG2 is expressed not only by glioma cells and by oligodendrocyte progenitors, but also by pericytes associated with the tumor microvasculature. The proteoglycan may therefore promote tumor vascularization and recruitment of normal progenitors to the tumor mass, in addition to mediating expansion of the transformed cell population. Along with potentiating growth factor signaling and serving as a cell surface receptor for extracellular matrix components, NG2 also has the ability to mediate activation of b-1 integrins. These molecular interactions allow the proteoglycan to contribute to critical processes such as cell proliferation, cell motility and cell survival.

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Section: Ng2 Expression In Gliomassupporting

confidence: 88%

A role for the NG2 proteoglycan in glioma progression

Stallcup

Huang

2008

Cell Adhesion & Migration

123

138

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“…NG2, a transmembrane chondroitin sulfate proteoglycan, is expressed by activated pericytes and vascular mural cells, but not endothelial cells. 22,23 As expected for pericytes, cells expressing NG2 in the colonies were directly adjacent to endothelial cells expressing CD31. Taking into account the differences in Figure 2.…”

Section: Cancer Cell Biologysupporting

confidence: 55%

G‐CSF rescues tumor growth and neo‐angiogenesis during liver metastasis under host angiopoietin‐2 deficiency

Im¹,

Tapmeier²,

Balathasan³

et al. 2012

Intl Journal of Cancer

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Suppression of neo‐angiogenesis is a clinically used anti‐tumor strategy with new targets such as angiopoietin‐2 (Ang2) being proposed. However, the functions of Ang2 in vascular remodeling, inflammation and tumor growth are not consistent. We examined effect of depletion of host Ang2 on liver colony formation using Ang2 deficient (Ang2−/−) mice. Surprisingly, the metastatic colonies formed in Ang2−/− mice were larger than those in the wild type. These colonies had greater vascular density with more pericyte coverage than the vessels in liver colonies in the wild type. Liver VEGF concentration in both genotypes was equivalent, and thus, the differences appeared VEGF independent. However, after colony formation, the serum concentration of granulocyte‐colony stimulating factor (G‐CSF) and CXCL1 in Ang2−/− mice was 12 and 6 times greater than after colony formation in wild type. Increase of these two cytokines was associated with two times greater numbers of neutrophils recruited to the liver. Two times more Tie2+/CD11b+/CD31− cells were present in the tumors in Ang2−/− than in the wild type livers. These results suggest that the depletion of host Ang2 induced compensatory VEGF‐independent angiogenic mechanisms and thus enhanced liver metastatic colony growth and colony vascularity. They further indicate organotypic differences in response to tumor metastasis. In contrast, Ang2 deficiency inhibited tumor growth during metastatic colony formation in the lung, consistent with the reports of decreased pulmonary seeding of tumor cells after pharmacological inhibition of Ang2. Further studies are thus required to assess the effects of pharmacological Ang2 blockade for cancer patients particularly in the liver.

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“…Coupled with our documentation of the early participation of NG2-positive pericytes during neovascularization [17], these observations suggest the possibility that pericyte-derived factors or NG2-dependent sequestration of growth factors might act to promote the proliferation of endothelial cells. Alternatively, the ability of NG2 to neutralize the growthinhibitory effects of angiostatin [22,57] may promote endothelial cell proliferation in the wild type mouse, an effect that would be absent in the NG2 null mouse.…”

Section: Discussionmentioning

confidence: 99%

Pathological angiogenesis is reduced by targeting pericytes via the NG2 proteoglycan

2004

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The NG2 proteoglycan is expressed by nascent pericytes during the early stages of angiogenesis. To investigate the functional role of NG2 in neovascularization, we have compared pathological retinal and corneal angiogenesis in wild type and NG2 null mice. During ischemic retinal neovascularization, ectopic vessels protruding into the vitreous occur twice as frequently in wild type retinas as in NG2 null retinas. In the NG2 knock-out retina, proliferation of both pericytes and endothelial cells is significantly reduced, and the pericyte:endothelial cell ratio falls to 0.24 from the wild type value of 0.86. Similarly, bFGF-induced angiogenesis is reduced more than four-fold in the NG2 null cornea compared to that seen in the wild type retina. Significantly, NG2 antibody is effective in reducing angiogenesis in the wild type cornea, suggesting that the proteoglycan can be an effective target for anti-angiogenic therapy. These experiments therefore demonstrate both the functional importance of NG2 in pericyte development and the feasibility of using pericytes as antiangiogenic targets. Keywords

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The glial precursor proteoglycan, NG2, is expressed on tumour neovasculature by vascular pericytes in human malignant brain tumours

Cited by 69 publications

References 59 publications

A role for the NG2 proteoglycan in glioma progression

A role for the NG2 proteoglycan in glioma progression

G‐CSF rescues tumor growth and neo‐angiogenesis during liver metastasis under host angiopoietin‐2 deficiency

Pathological angiogenesis is reduced by targeting pericytes via the NG2 proteoglycan

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