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鉴定小儿脉络丛乳头状瘤中的血管生成因子

Identifying Angiogenic Factors in Pediatric Choroid Plexus Papillomas.

作者信息

Syed Sulaiman Nurfarhanah Bte, Sng Sofiah M Y, Merchant Khurshid Z, Ng Lee Ping, Low David C Y, Seow Wan Tew, Low Sharon Y Y

机构信息

Neurosurgical Service, KK Women's and Children's Hospital, Singapore 229899, Singapore.

Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore 229899, Singapore.

出版信息

NeuroSci. 2025 Aug 11;6(3):76. doi: 10.3390/neurosci6030076.

Abstract

(1) Background: Choroid plexus papillomas (CPPs) are rare brain tumors that tend to occur in very young children. Mechanisms of CPP development remain unelucidated. Separately, the process of angiogenesis has been implicated in other primary brain tumors. We hypothesize that angiogenesis is a hallmark of CPP biology. This study aims to identify and validate angiogenic factors in CPPs. (2) Methods: Cerebrospinal fluid (CSF) and CPP tumor samples are collected. A multiplex immunoassay panel is used to identify differentially expressed cytokines in the CSF samples. Concurrently, patient-derived primary cell cultures and their supernatants are derived from CPP samples. Targeted proteome blot arrays and human umbilical vein endothelial cell (HUVEC) angiogenesis assays are used for validation studies. (3) Results: CSF profiling showed higher expressions of VEGF-A, MCP-1, MMP-1, TNF-α, and CD40L in CPP patient samples versus non-tumor controls. Next, assessment via online protein-protein network platforms reports that these cytokines are associated with endothelial cell regulation. Using an angiogenesis-focused approach, CPP-derived cell lines and supernatants showed similarly higher expressions of VEGF, MCP-1, and MMP-1. Next, sprouting of nodes and tubule formation were observed in HUVEC angiogenesis assay cultures when conditioned CPP cell culture media was added. (4) Conclusions: This proof-of-concept study demonstrates potential to explore angiogenesis in CPP.

摘要

(1) 背景:脉络丛乳头状瘤(CPPs)是罕见的脑肿瘤,多发生于幼儿。CPPs的发病机制尚不清楚。另外,血管生成过程与其他原发性脑肿瘤有关。我们假设血管生成是CPP生物学的一个标志。本研究旨在识别和验证CPPs中的血管生成因子。(2) 方法:收集脑脊液(CSF)和CPP肿瘤样本。使用多重免疫分析试剂盒识别CSF样本中差异表达的细胞因子。同时,从CPP样本中获取患者来源的原代细胞培养物及其上清液。使用靶向蛋白质印迹阵列和人脐静脉内皮细胞(HUVEC)血管生成试验进行验证研究。(3) 结果:CSF分析显示,与非肿瘤对照相比,CPP患者样本中VEGF-A、MCP-1、MMP-1、TNF-α和CD40L的表达更高。接下来,通过在线蛋白质-蛋白质网络平台评估报告称,这些细胞因子与内皮细胞调节有关。采用聚焦血管生成的方法,CPP来源的细胞系和上清液中VEGF、MCP-1和MMP-1的表达同样较高。接下来,当添加经条件培养的CPP细胞培养基时,在HUVEC血管生成试验培养物中观察到节点发芽和小管形成。(4) 结论:这项概念验证研究证明了探索CPP血管生成的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f44/12372068/185b3f5adb7b/neurosci-06-00076-g0A1.jpg

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