Antigenic and Genotypic Similarity between Primary Glioblastomas and Their Derived Neurospheres

Caldera, Valentina; Mellai, Marta; Annovazzi, Laura; Piazzi, Angela; Lanotte, Michele; Cassoni, Paola; Schiffer, Davide

doi:10.1155/2011/314962

Cited by 25 publications

(52 citation statements)

References 47 publications

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“…Surgical tumor tissue was processed as described in [23]. Culture conditions were Dulbecco's modified Eagle's medium (DMEM)/F-12 with 10 ng/mL bFGF (basic fibroblast growth factor) and 20 ng/mL EGF (epidermal growth factor) for neurospheres (NS), and DMEM with 10% fetal bovine serum (FBS) for adherent cells (AC).…”

Section: Methodsmentioning

confidence: 99%

Promoter Hypermethylation of theEMP3Gene in a Series of 229 Human Gliomas

Mellai

Piazzi

Caldera

et al. 2013

BioMed Research International

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The epithelial membrane protein 3 (EMP3) is a candidate tumor suppressor gene in the critical region 19q13.3 for several solid tumors, including tumors of the nervous systems. The aim of this study was to investigate the EMP3 promoter hypermethylation status in a series of 229 astrocytic and oligodendroglial tumors and in 16 GBM cell lines. The analysis was performed by methylation-specific PCR and capillary electrophoresis. Furthermore, the EMP3 expression at protein level was evaluated by immunohistochemistry and Western blotting analysis. Associations of EMP3 hypermethylation with total 1p/19q codeletion, MGMT promoter hypermethylation, IDH1/IDH2 and TP53 mutations, and EGFR amplification were studied, as well as its prognostic significance. The EMP3 promoter hypermethylation has been found in 39.5% of gliomas. It prevailed in low-grade tumors, especially in gliomas with an oligodendroglial component, and in sGBMs upon pGBMs. In oligodendroglial tumors, it was strongly associated with both IDH1/IDH2 mutations and total 1p/19q codeletion and inversely with EGFR gene amplification. No association was found with MGMT hypermethylation and TP53 mutations. In the whole series, the EMP3 hypermethylation status correlated with 19q13.3 loss and lack of EMP3 expression at protein level. A favorable prognostic significance on overall survival of the EMP3 promoter hypermethylation was found in patients with oligodendroglial tumors.

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Section: Methodsmentioning

confidence: 99%

Promoter Hypermethylation of theEMP3Gene in a Series of 229 Human Gliomas

Mellai

Piazzi

Caldera

et al. 2013

BioMed Research International

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“…Both are composed of a high number of cells positive for stemness markers such as CD133, Nestin, SOX2, and RE-1-silencing transcription factor (REST), and have a high proliferation index ( Figure 5E,F) [163,187,188]. GSCs can be conceived as deriving from dedifferentiated tumor cells that acquired stemness properties [189]; they would be concentrated in the above mentioned malignant tumor areas where circumscribed necroses develop because of the vascular insufficiency. It is likely that GSCs around necroses represent the quota of GSCs that populated the hyperproliferating areas and remained unaffected by necrosis development.…”

Section: Hypoxia and Necroses -Perinecrotic Nichesmentioning

confidence: 99%

“…It is likely that GSCs around necroses represent the quota of GSCs that populated the hyperproliferating areas and remained unaffected by necrosis development. The palisadings themselves would be the remnants of hyperproliferating areas, spared by necrosis [45,189]. …”

Section: Hypoxia and Necroses -Perinecrotic Nichesmentioning

confidence: 99%

“…The significance conferred to GSCs in perinecrotic position as dedifferentiated tumor cells which reached stemness beyond a certain point of dedifferentiation, cannot be recognized to GSCs in perivascular niches [45,189]. Letting aside the transdifferentiation of tumor cells into endothelial cells, which did not received sufficient support, another point of link between the two microenvironments is represented by cell migration through EMT that is promoted by hypoxia and bound to GSCs [155].…”

Section: Functions Of the Niches In The Tumor And Their Interdependencementioning

confidence: 99%

“…The most important question in this topic is the occurrence of circumscribed necroses in the tumor areas with the highest malignant phenotype including both avascular districts and districts with a high vessel density, so that perinecrotic niches appear to be associated with perivascular niches to characterize these malignant areas [45,189,195].…”

Section: Functions Of the Niches In The Tumor And Their Interdependencementioning

confidence: 99%

See 2 more Smart Citations

Tumor Microenvironment — Perivascular and Perinecrotic Niches

Schiffer¹,

Mellai²,

Annovazzi³

et al. 2015

Molecular Considerations and Evolving Surgical Management Issues in the Treatment of Patients With a Brain Tumor

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SEL1L plays a major role in human malignant gliomas

Mellai

Annovazzi

Boldorini

et al. 2019

The Journal of Pathology CR

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Suppressor of Lin‐12‐like (C. elegans) (SEL1L) participates in the endoplasmic reticulum‐associated protein degradation pathway, malignant transformation and stem cell biology. We explored the role of SEL1L in 110 adult gliomas, of different molecular subtype and grade, in relation to cell proliferation, stemness, glioma‐associated microglia/macrophages (GAMs), prognostic markers and clinical outcome. SEL1L protein expression was assessed by immunohistochemistry and Western blotting. Genetic and epigenetic alterations were detected by molecular genetics techniques. SEL1L was overexpressed in anaplastic gliomas (World Health Organization [WHO] grade III) and in glioblastoma (GB, WHO grade IV) with the highest labelling index (LI) in the latter. Immunoreactivity was significantly associated with histological grade (p = 0.002) and cell proliferation index Ki‐67/MIB‐1 (p = 0.0001). In GB, SEL1L co‐localised with stemness markers Nestin and Sox2. Endothelial cells and vascular pericytes of proliferative tumour blood vessels expressed SEL1L suggesting a role in tumour neo‐vasculature. GAMs consistently expressed SEL1L. SEL1L overexpression was significantly associated with TERT promoter mutations (p = 0.0001), EGFR gene amplification (p = 0.0013), LOH on 10q (p = 0.0012) but was mutually exclusive with IDH1/2 mutations (p = 0.0001). SEL1L immunoreactivity correlated with tumour progression and cell proliferation, conditioning poor patient survival and response to therapy. This study emphasises SEL1L as a potential biomarker for the most common subgroup of TERT mutant/EGFR amplified/IDH‐WT GBs.

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Antigenic and Genotypic Similarity between Primary Glioblastomas and Their Derived Neurospheres

Cited by 25 publications

References 47 publications

Promoter Hypermethylation of theEMP3Gene in a Series of 229 Human Gliomas

Promoter Hypermethylation of theEMP3Gene in a Series of 229 Human Gliomas

Tumor Microenvironment — Perivascular and Perinecrotic Niches

SEL1L plays a major role in human malignant gliomas

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