NG2 expression regulates vascular morphology and function in human brain tumours

Brekke, Cecilie; Lundervold, Arvid; Enger, Per Øyvind; Brekken, Christian; Stålsett, E.; Pedersen, Torben Bach; Haraldseth, Olav; Krüger, Per Gøran; Bjerkvig, Rolf; Chekenya, Martha

doi:10.1016/j.neuroimage.2005.08.026

Cited by 37 publications

(42 citation statements)

References 54 publications

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“…NG2 proteoglycan is a cell surface molecule and a prominent component of pericytes in tumor microvessels. It has the potential to affect tumor progression by contributing to pericyte recruitment and pericyte-endothelial cell interactions (Ozerdem et al, 2002;Brekke et al, 2006). In contrast, ␣-SMA has been reported as a marker of mature mural cells including both pericytes and smooth muscle cells (Yonenaga et al, 2005).…”

Section: Resultsmentioning

confidence: 99%

Activation of Alternate Prosurvival Pathways Accounts for Acquired Sunitinib Resistance in U87MG Glioma Xenografts

Zhou

Mazloom

et al. 2012

J Pharmacol Exp Ther

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Acquired drug resistance represents a major obstacle to using sunitinib for the treatment of solid tumors. Here, we examined the cellular and molecular alterations in tumors that are associated with acquired brain tumor resistance to sunitinib by using an in vivo model. U87MG tumors obtained from nude mice that received sunitinib (40 mg/kg/day) for 30 days were classified into sunitinib-sensitive and -resistant groups based on tumor volume and underwent targeted gene microarray and protein array analyses. The expression of several angiogenesisassociated genes was significantly modulated in sunitinibtreated tumors compared with those in control tumors (p Ͻ 0.05), whereas no significant differences were observed between sunitinib-sensitive and -resistant tumors (p Ͼ 0.05). Tumor vasculature based on microvessel density, neurogenin 2 chondroitin sulfate proteoglycan density, and ␣-smooth muscle actin density was also similar in sunitinib-treatment groups (p Ͼ 0.05). The moderate increase in unbound sunitinib tumor-toplasma area-under-the-curve ratio in sunitinib-resistant mice was accompanied by up-regulated ATP-binding cassette G2 expression in tumor. The most profound difference between the sunitinib-sensitive and -resistant groups was found in the expression of several phosphorylated proteins involved in intracellular signaling. In particular, phospholipase C-␥1 phosphorylation in sunitinib-resistant tumors was up-regulated by 2.6-fold compared with that in sunitinib-sensitive tumors (p Ͻ 0.05). In conclusion, acquired sunitinib resistance in U87MG tumors is not associated with revascularization in tumors, but rather with the activation of alternate prosurvival pathways involved in an escape mechanism facilitating tumor growth and possibly insufficient drug uptake in tumor cells caused by an up-regulated membrane efflux transporter.

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Section: Resultsmentioning

confidence: 99%

Activation of Alternate Prosurvival Pathways Accounts for Acquired Sunitinib Resistance in U87MG Glioma Xenografts

Zhou

Mazloom

et al. 2012

J Pharmacol Exp Ther

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“…Notably, the upregulation of nestin at the periphery of the tumor bulk and in migrating glioma cells suggests a role for nestinexpressing cells in glioma invasion (12). Moreover, NG2-positive glioma cells have been shown to mediate angiogenesis and regulate vascular morphology in brain tumors (13,14). Finally, glioma cells expressing immature markers associated with stem cells and progenitors confer radioresistance and chemoresistance (15,16), which is a typical feature in malignant gliomas.…”

Section: Discussionmentioning

confidence: 99%

Glioma Cell Populations Grouped by Different Cell Type Markers Drive Brain Tumor Growth

et al. 2010

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Although CD133 has been proposed as a marker for brain tumor-initiating cells, studies show that a tumorigenic potential exists among CD133− glioma cells as well. However, it is not established whether the ability of CD133 − cells to form tumors is a property confined to a small subpopulation, rather than a common trait associated with most glioma cell types. Thus, we used lentiviral vectors expressing green fluorescent protein under lineage-specific promoters to identify CD133 − glioma cells expressing Nestin, glial fibrillary acidic protein (GFAP), and neuron-specific enolase (NSE). Flow cytometry analysis showed the presence of CD133 − subpopulations expressing these markers in glioma cell lines and in primary cultures from human glioblastoma (GBM) biopsies. Moreover, analysis of cell cycle distribution showed that subgroups expressing Nestin, GFAP, and NSE uniformly contained actively cycling cells, when cultured in serum-containing medium and stem cell medium. These subpopulations were fluorescence-activated cell sorted from CD133 − U373 glioma cells and implanted intracerebrally in severe combined immunodeficient mice. Moreover, we implanted Nestin-, GFAP-, and NSE-positive glioma cells sorted from a human GBM biopsy, following removal of CD133-positive cells. All the CD133 − subpopulations produced tumors, with no significant differences in survival or tumor take rates. However, there was a trend toward lower take rates for CD133 − glioma subpopulations expressing GFAP and NSE. These findings suggest that the ability to form tumors may be a general trait associated with different glioma cell phenotypes, rather than a property limited to an exclusive subpopulation of glioma stem cells. Cancer Res; 70(11); 4274-9. ©2010 AACR.

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“…32,72,82,92 Intriguingly, expression of NG2 by glioma cells themselves has also been noted to have important effects on the characteristics of the glioma vasculature. 81,93 …”

Section: Ng2 Expression In Tumor Vasculaturementioning

confidence: 99%

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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NG2 expression regulates vascular morphology and function in human brain tumours

Cited by 37 publications

References 54 publications

Activation of Alternate Prosurvival Pathways Accounts for Acquired Sunitinib Resistance in U87MG Glioma Xenografts

Activation of Alternate Prosurvival Pathways Accounts for Acquired Sunitinib Resistance in U87MG Glioma Xenografts

Glioma Cell Populations Grouped by Different Cell Type Markers Drive Brain Tumor Growth

A role for the NG2 proteoglycan in glioma progression

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