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软骨素硫酸盐蛋白聚糖 4（NG2/CSPG4）在低级别和高级别神经胶质瘤中的定位。

Chondroitin Sulphate Proteoglycan 4 (NG2/CSPG4) Localization in Low- and High-Grade Gliomas.

机构信息

Dipartimento di Scienze della Salute, Scuola di Medicina, Università del Piemonte Orientale (UPO), Via Solaroli 17, 28100 Novara, Italy.

Centro Interdipartimentale di Ricerca Traslazionale sulle Malattie Autoimmuni e Allergiche (CAAD), Università del Piemonte Orientale (UPO), Corso Trieste 15A, 28100 Novara, Italy.

出版信息

Cells. 2020 Jun 24;9(6):1538. doi: 10.3390/cells9061538.

DOI:10.3390/cells9061538
PMID:32599896
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7349878/
Abstract

BACKGROUND

Neuron glial antigen 2 or chondroitin sulphate proteoglycan 4 (NG2/CSPG4) is expressed by immature precursors/progenitor cells and is possibly involved in malignant cell transformation. The aim of this study was to investigate its role on the progression and survival of sixty-one adult gliomas and nine glioblastoma (GB)-derived cell lines.

METHODS

NG2/CSPG4 protein expression was assessed by immunohistochemistry and immunofluorescence. Genetic and epigenetic alterations were detected by molecular genetic techniques.

RESULTS

NG2/CSPG4 was frequently expressed in IDH-mutant/1p19q-codel oligodendrogliomas (59.1%) and IDH-wild type GBs (40%) and rarely expressed in IDH-mutant or IDH-wild type astrocytomas (14.3%). Besides tumor cells, NG2/CSPG4 immunoreactivity was found in the cytoplasm and/or cell membranes of reactive astrocytes and vascular pericytes/endothelial cells. In GB-derived neurospheres, it was variably detected according to the number of passages of the in vitro culture. In GB-derived adherent cells, a diffuse positivity was found in most cells. NG2/CSPG4 expression was significantly associated with gene amplification ( = 0.0005) and poor prognosis ( = 0.016) in astrocytic tumors.

CONCLUSION

The immunoreactivity of NG2/CSPG4 provides information on the timing of the neoplastic transformation and could have prognostic and therapeutic relevance as a promising tumor-associated antigen for antibody-based immunotherapy in patients with malignant gliomas.

摘要

背景

神经胶质抗原 2 或软骨素硫酸蛋白聚糖 4（NG2/CSPG4）由未成熟前体细胞/祖细胞表达，可能参与恶性细胞转化。本研究旨在探讨其在 61 例成人胶质瘤和 9 例胶质母细胞瘤（GB）衍生细胞系中的进展和生存中的作用。

方法

通过免疫组织化学和免疫荧光法评估 NG2/CSPG4 蛋白表达。采用分子遗传学技术检测遗传和表观遗传改变。

结果

NG2/CSPG4 在 IDH 突变/1p19q 共缺失少突胶质细胞瘤（59.1%）和 IDH 野生型 GB（40%）中频繁表达，而在 IDH 突变型或 IDH 野生型星形细胞瘤中很少表达（14.3%）。除肿瘤细胞外，反应性星形胶质细胞和血管周细胞/内皮细胞的细胞质和/或细胞膜中也可见 NG2/CSPG4 免疫反应性。在 GB 衍生的神经球中，根据体外培养的传代数，其表达情况存在差异。在 GB 衍生的贴壁细胞中，大多数细胞呈弥漫性阳性。NG2/CSPG4 表达与 基因扩增显著相关（ = 0.0005），在星形细胞瘤中与预后不良显著相关（ = 0.016）。

结论

NG2/CSPG4 的免疫反应性提供了肿瘤转化时间的信息，并可能具有预后和治疗相关性，作为恶性神经胶质瘤患者抗体为基础的免疫治疗的有前途的肿瘤相关抗原。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64ec/7349878/3c829dab544b/cells-09-01538-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64ec/7349878/b2df31c9e5c4/cells-09-01538-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64ec/7349878/69970f52b2fa/cells-09-01538-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64ec/7349878/1d145e76f4d1/cells-09-01538-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64ec/7349878/8e76643edb1e/cells-09-01538-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64ec/7349878/3c829dab544b/cells-09-01538-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64ec/7349878/b2df31c9e5c4/cells-09-01538-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64ec/7349878/69970f52b2fa/cells-09-01538-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64ec/7349878/1d145e76f4d1/cells-09-01538-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64ec/7349878/8e76643edb1e/cells-09-01538-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64ec/7349878/3c829dab544b/cells-09-01538-g005.jpg

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