Immunohistochemical evaluation of the microvascular density through the expression of TGF‐β (CD 105/endoglin) and CD 34 receptors and expression of the vascular endothelial growth factor (VEGF) in oligodendrogliomas

Netto, Gabriel Corteze; Bleil, Cristina Birlem; Hilbig, Arlete; Coutinho, Lígia Maria Barbosa

doi:10.1111/j.1440-1789.2007.00825.x

Cited by 35 publications

(18 citation statements)

References 42 publications

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“…Vasculature is a source of signals for CNS stem cell self-renewal 33 , but is also a delivery vehicle for oxygen, thereby presenting two potentially antagonistic signals for precursor proliferation 34 . We performed immunohistochemical analyses of MDB tumor tissues to determine if neural precursor numbers co-varied with tumor areas of low or high microvascular density (MVD), measured by CD34 expression 35 . Staining indicated that MDB areas with low MVD had high HIF-1α expression (Suppl.…”

Section: Resultsmentioning

confidence: 99%

Interaction of Hypoxia-Inducible Factor-1α and Notch Signaling Regulates Medulloblastoma Precursor Proliferation and Fate

et al. 2010

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Medulloblastoma (MDB) is the most common brain malignancyof childhood. It is currently thought that MDB arises from aberrantly functioning stem cells in the cerebellum that fail to maintain proper control of self-renewal. Additionally, it has been reported that MDB cells display higher endogenous Notch signaling activation, known to promote the survival and proliferation of neoplastic neural stem cells and to inhibit their differentiation. While interaction between Hypoxia Inducible Factor-1α (HIF-1α) and Notch signalling is required to maintain normal neural precursors in an undifferentiated state, an interaction has not been identified in MDB. Here we investigate whether hypoxia, through HIF-1α stabilization, modulates Notch1 signaling in primary MDB-derived cells. Our results indicate that MDB-derived precursor cells require hypoxic conditions for in vitro expansion, whereas acute exposure to 20% oxygen induces tumor cell differentiation and death through inhibition of Notch signaling. Importantly, stimulating Notch1 activation with its ligand Dll4 under hypoxic conditions leads to expansion of MDB-derived CD133+ and nestin+ precursors, suggesting a regulatory effect on stem cells. In contrast, MDB cells undergo neuronal differentiation when treated with γ-secretase inhibitor, which prevents Notch activation. These results suggest that hypoxia, by maintaining Notch1 in its active form, preserves MDB stem cell viability and expansion.

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Section: Resultsmentioning

confidence: 99%

Interaction of Hypoxia-Inducible Factor-1α and Notch Signaling Regulates Medulloblastoma Precursor Proliferation and Fate

et al. 2010

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“…Pericytes (also indicated as smooth muscle cells or mural cells) form an incomplete layer around the endothelial cells (32). CD105 is a marker for activated endothelial cells taking part in neoangiogenesis not only in gliomas but also in other tumors (13, 20, 23). Most available data on the cells involved in neoangiogenesis concern endothelial cells and factors regulating their proliferation (11, 16).…”

Section: Introductionmentioning

confidence: 99%

Expression Sites of Colligin 2 in Glioma Blood Vessels

Mustafa¹,

Weiden²,

Zheng³

et al. 2009

Brain Pathology

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In a previous study using state-of-the-art proteomic techniques, we identified colligin 2 (HSP47) as a glioma blood vessel-specific protein. In the present study we precisely localized the expression of colligin 2 in the blood vessels of diffusely infiltrating gliomas and relate the expression to the distinct cellular components of the vessels by using multiple immunolabeling and confocal microscopy. We grouped the glioma blood vessels into morphological categories ranging from normal looking capillaries to vessels with hypertrophic and sclerotic changes. The expression patterns of various markers of endothelial and pericytic differentiation were correlated with the position of the cells in the vessels and the expression of colligin 2. We found that colligin 2 is expressed in all categories of glioma blood vessels in cells with endothelial and pericytic lineage. Expression of colligin 2 was also found in cells scattered around blood vessels and in few glial fibrillary acidic protein-positive cells within the blood vessels. There is overlap in the expression of colligin 2 and the collagens type I and IV for which colligin 2 is a chaperon. We conclude that colligin 2 is expressed in all cellular components of glioma blood vessels and may serve as a general marker for active angiogenesis.

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“…5 In recent years, studies have demonstrated that CD34-positive vessels play pivotal roles in the development of gliomas and have an influence on the malignant severity. 10,11,13 There have been a few reports that have comprehensively described the significance of CD34 in glioma patients and the specific roles of CD34 in the grading and prognosis of gliomas remain unclear. Therefore, it is unclear whether CD34 can be used as a marker of WHO grades in gliomas.…”

Section: Discussionmentioning

confidence: 99%

“…Rahmah et al 11 found that high-grade gliomas showed higher expression of CD34, which suggested that high-grade glioma may have higher densities of vessel, whereas Netto et al 13 found high expression levels of CD34 in the endothelial cells in their oligodendroglioma study. They did not find any significant correlation to the grades of oligodendroglioma.…”

Section: Introductionmentioning

confidence: 98%

“…They did not find any significant correlation to the grades of oligodendroglioma. 13 We carried out a meta-analysis to make clear the practical significance of CD34 and resolve the between-study heterogeneity. This is possible because a meta-analysis is able to avoid the potential bias of sources such as with the selected populations and study methodology.…”

Section: Introductionmentioning

confidence: 99%

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CD34 Over-Expression is Associated With Gliomas’ Higher WHO Grade

Kong

Guan²,

Ma³

et al. 2016

Medicine

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CD34 is a transmembrane phosphoglycoprotein that was first identified on hematopoietic stem and progenitor cells. CD34 is known as an optimum marker for microvascular density studies and it is positively stained in pathological and physiologic vessels. The use of CD34 for the prognosis, diagnosis, and treatment of neoplasms has been increasingly discussed. The implications and utilities of CD34 in WHO grades of gliomas and its prognosis have been reported rarely. Also, the WHO grades and prognosis researches remains unclear and controversial. A meta-analysis is the best choice for drawing a convincing conclusion.Several databases were searched. We carefully assess the relevant articles and standard mean differences (SMDs) with 95% confidence intervals (95% CIs) were estimated in terms of the relationship between CD34 expression levels with gliomas’ WHO grades, patients’ ages and gender. We used the Galbraith figure, the I2 test, and Cochran Q test to evaluate the heterogeneity of the included studies. A sensitivity analysis was conducted to assess the pooled results’ stability. A Contour-enhanced funnel plot evaluation was made to assess potential publication bias. Ethics review and approval was not necessary because the meta-analysis did not involve any direct human trials or animal experiments.There were 12 eligible studies, including 684 patients who were considered in the present meta-analysis. All of them were conducted in China. CD34 overexpression in glioma tissues was associated closely, according to the pooled SMD, with higher WHO grade (III + IV) (SMD -1.503, 95% CI -1.685 to -1.321; P = 0.000). There were no significant associations between CD34 and age (SMD -0.223, 95% CI -0.602 to 0.156; P = 0.248) and CD34 and gender (SMD -0.059, 95% CI -0.439, 0.321; P = 0.761). No publication bias was detected according to Contour-enhanced funnel plot.Our results suggested that CD34 overexpression is associated with higher WHO grades of gliomas. CD34 may serve as a potential diagnostic and prognostic marker, or it could be a useful therapy target.

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Immunohistochemical evaluation of the microvascular density through the expression of TGF‐β (CD 105/endoglin) and CD 34 receptors and expression of the vascular endothelial growth factor (VEGF) in oligodendrogliomas

Cited by 35 publications

References 42 publications

Interaction of Hypoxia-Inducible Factor-1α and Notch Signaling Regulates Medulloblastoma Precursor Proliferation and Fate

Interaction of Hypoxia-Inducible Factor-1α and Notch Signaling Regulates Medulloblastoma Precursor Proliferation and Fate

Expression Sites of Colligin 2 in Glioma Blood Vessels

CD34 Over-Expression is Associated With Gliomas’ Higher WHO Grade

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