Identification of established and novel extracellular matrix components in glioblastoma as targets for angiogenesis and prognosis.

IF 1.6 4区医学 Q3 CLINICAL NEUROLOGY

Neurogenetics Pub Date : 2024-07-01 Epub Date: 2024-05-22 DOI:10.1007/s10048-024-00763-x

Lucas Cunha Barbosa, Gabriel Cardoso Machado, Manoela Heringer, Valéria Pereira Ferrer

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引用次数: 0

Abstract

Glioblastomas (GBM) are aggressive tumors known for their heterogeneity, rapid proliferation, treatment resistance, and extensive vasculature. Angiogenesis, the formation of new vessels, involves endothelial cell (EC) migration and proliferation. Various extracellular matrix (ECM) molecules regulate EC survival, migration, and proliferation. Culturing human brain EC (HBMEC) on GBM-derived ECM revealed a decrease in EC numbers compared to controls. Through in silico analysis, we explored ECM gene expression differences between GBM and brain normal glia cells and the impact of GBM microenvironment on EC ECM transcripts. ECM molecules such as collagen alpha chains (COL4A1, COL4A2, p < 0.0001); laminin alpha (LAMA4), beta (LAMB2), and gamma (LAMC1) chains (p < 0.0005); neurocan (NCAN), brevican (BCAN) and versican (VCAN) (p < 0.0005); hyaluronan synthase (HAS) 2 and metalloprotease (MMP) 2 (p < 0.005); MMP inhibitors (TIMP1-4, p < 0.0005), transforming growth factor beta-1 (TGFB1) and integrin alpha (ITGA3/5) (p < 0.05) and beta (ITGB1, p < 0.0005) chains showed increased expression in GBM. Additionally, GBM-influenced EC exhibited elevated expression of COL5A3, COL6A1, COL22A1 and COL27A1 (p < 0.01); LAMA1, LAMB1 (p < 0.001); fibulins (FBLN1/2, p < 0.01); MMP9, HAS1, ITGA3, TGFB1, and wingless-related integration site 9B (WNT9B) (p < 0.01) compared to normal EC. Some of these molecules: COL5A1/3, COL6A1, COL22/27A1, FBLN1/2, ITGA3/5, ITGB1 and LAMA1/B1 (p < 0.01); NCAN, HAS1, MMP2/9, TIMP1/2 and TGFB1 (p < 0.05) correlated with GBM patient survival. In conclusion, this study identified both established and novel ECM molecules regulating GBM angiogenesis, suggesting NCAN and COL27A1 are new potential prognostic biomarkers for GBM.

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鉴定胶质母细胞瘤中作为血管生成和预后靶点的既有和新型细胞外基质成分。

胶质母细胞瘤（GBM）是一种侵袭性肿瘤，以其异质性、快速增殖、耐药性和广泛的血管而闻名。血管生成（新血管的形成）涉及内皮细胞（EC）的迁移和增殖。各种细胞外基质（ECM）分子可调节内皮细胞的存活、迁移和增殖。与对照组相比，在源自 GBM 的 ECM 上培养人脑 EC（HBMEC）会导致 EC 数量减少。通过硅学分析，我们探讨了 GBM 和脑正常胶质细胞之间的 ECM 基因表达差异，以及 GBM 微环境对 ECCM 转录本的影响。ECM分子如胶原蛋白α链（COL4A1、COL4A2、p

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来源期刊

Neurogenetics 医学-临床神经学

CiteScore

3.90

自引率

0.00%

发文量

审稿时长

6 months

期刊介绍： Neurogenetics publishes findings that contribute to a better understanding of the genetic basis of normal and abnormal function of the nervous system. Neurogenetic disorders are the main focus of the journal. Neurogenetics therefore includes findings in humans and other organisms that help understand neurological disease mechanisms and publishes papers from many different fields such as biophysics, cell biology, human genetics, neuroanatomy, neurochemistry, neurology, neuropathology, neurosurgery and psychiatry. All papers submitted to Neurogenetics should be of sufficient immediate importance to justify urgent publication. They should present new scientific results. Data merely confirming previously published findings are not acceptable.