The Monocarboxylate Transporters MCT1 and MCT4 Are Highly Expressed in Glioblastoma and Crucially Implicated in the Pathobiology.

IF 1.3 4区 医学 Q4 CLINICAL NEUROLOGY
Neuropathology Pub Date : 2025-03-27 DOI:10.1111/neup.70006
Minakshi M Behera, Suvendu Purkait, Amit Ghosh, Mukund N Sable, Rabi Narayan Sahu, Gaurav Chhabra
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引用次数: 0

Abstract

Monocarboxylate transporters (MCTs) are crucially implicated in cancer cell metabolism by transporting lactate/H+ ions and thus regulating the pH of the microenvironment. We assessed MCT1 and MCT4 expression in 98 cases of adult-type hemispheric Glioblastomas (GBMs) (IDH wild-type), along with 51 cases of IDH-mutant astrocytic and oligodendroglial tumors (grade 2-4) for comparison. U87MG and LN229 cell lines were used for in vitro analysis. Both MCT-1 and MCT-4 showed significantly higher expression in GBMs on immunohistochemistry than in IDH-mutated gliomas, which mostly showed weak or negative immunoreactivity. The mRNA expression was also in a similar line. Interestingly, in all areas of the pathological endothelial proliferation of grade 4 tumors, there was MCT-1 loss of expression, unlike the nonproliferating endothelium. High MCT1/4 expression was associated with shorter overall survival in all gliomas together but not in GBM separately. Syrosingopine, a dual MCT1/4 inhibitor, showed significant antitumor effects in both the glioma cell lines, including dose-dependent cytotoxicity, increased apoptosis, and decreased migration/invasion. The results indicated the role of MCT1/4 in the pathobiology of GBM and the diagnostic utility at the immunohistochemical level. Syrosingopine, an antihypertensive agent with good CNS penetration and previously used in different malignancies, may be an essential therapeutic adjunct in GBM.

单羧酸转运体MCT1和MCT4在胶质母细胞瘤中高表达并与病理生物学密切相关。
单羧酸转运体(mct)通过运输乳酸/H+离子,从而调节微环境的pH值,在癌细胞代谢中起着至关重要的作用。我们评估了98例成人型半球胶质母细胞瘤(GBMs) (IDH野生型)以及51例IDH突变型星形细胞和少突胶质肿瘤(2-4级)的MCT1和MCT4表达进行比较。采用U87MG和LN229细胞系进行体外分析。免疫组化结果显示,MCT-1和MCT-4在GBMs中的表达均明显高于idh突变胶质瘤,且大多表现出弱或阴性的免疫反应性。mRNA的表达也在一条相似的线上。有趣的是,在4级肿瘤病理内皮增生的所有区域,与非增殖内皮不同,MCT-1表达缺失。在所有胶质瘤中,MCT1/4的高表达与较短的总生存期相关,而在单独的GBM中则无关。Syrosingopine是一种双重MCT1/4抑制剂,在两种胶质瘤细胞系中均显示出显著的抗肿瘤作用,包括剂量依赖性细胞毒性、增加细胞凋亡和减少迁移/侵袭。结果提示MCT1/4在GBM病理生物学中的作用及免疫组化水平上的诊断价值。Syrosingopine是一种抗高血压药物,具有良好的中枢神经穿透性,以前用于不同的恶性肿瘤,可能是GBM必不可少的治疗辅助药物。
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来源期刊
Neuropathology
Neuropathology 医学-病理学
CiteScore
4.10
自引率
4.30%
发文量
105
审稿时长
6-12 weeks
期刊介绍: Neuropathology is an international journal sponsored by the Japanese Society of Neuropathology and publishes peer-reviewed original papers dealing with all aspects of human and experimental neuropathology and related fields of research. The Journal aims to promote the international exchange of results and encourages authors from all countries to submit papers in the following categories: Original Articles, Case Reports, Short Communications, Occasional Reviews, Editorials and Letters to the Editor. All articles are peer-reviewed by at least two researchers expert in the field of the submitted paper.
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