SOX4 促进胶质母细胞瘤的血管异常,是改善给药的新靶点

IF 5 2区 医学 Q2 Medicine Translational Oncology Pub Date : 2024-09-16 DOI:10.1016/j.tranon.2024.102120
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引用次数: 0

摘要

胶质母细胞瘤(GBM)是成人中最常见的侵袭性原发性脑肿瘤,预后极差。血管异常是胶质母细胞瘤的特征之一,它通过增加缺氧、诱发危及生命的水肿和阻碍药物输送而加剧疾病的进展。然而,人们对血管异常的复杂机制仍缺乏足够的了解。在这里,我们揭示了 SOX4 在 GBM 血管异常中的关键作用。与配对正常脑组织的内皮细胞相比,人脑肿瘤的内皮细胞(ECs)中 SOX4 表达增加。在小鼠脑内皮细胞中敲除 SOX4 可抑制细胞迁移和增殖。此外,体外抑制脑EC细胞中的SOX4和体内有条件敲除肿瘤EC细胞中的SOX4会导致与血管异常有关的基因下调。值得注意的是,特异性消耗脑细胞中的 SOX4 能增强药物输送,提高肿瘤对 GBM 化疗药物的敏感性。综上所述,这些结果表明,SOX4 是 GBM 中肿瘤血管生成和血管异常的新型调节因子。我们的研究发现,SOX4 是一种潜在的血管治疗靶点,可改善 GBM 治疗的给药效果。
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SOX4 promotes vascular abnormality in glioblastoma and is a novel target to improve drug delivery

Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults with dismal prognosis. Vascular abnormality is a hallmark of GBM, and aggravates diseases progression by increasing hypoxia, inducing life-threaten edema and hindering drug delivery. Nonetheless, the intricate mechanism underlying vascular abnormality remains inadequately understood. Here, we revealed a key role of SOX4 on vascular abnormality in GBM. SOX4 expression was increased in endothelial cells (ECs) from human brain tumors compared with ECs from paired normal brain tissue. Knockdown of SOX4 in mouse brain ECs restrained cell migration and proliferation. Furthermore, in vitro suppression of SOX4 in brain ECs and in vivo conditional knockout of SOX4 in tumor ECs led to the downregulation of genes linked with vascular abnormality. Notably, specific depletion of SOX4 in ECs enhanced drug delivery and sensitive tumor to chemotherapeutic drugs in GBM. Taken together, these results demonstrated that SOX4 is a novel regulator for tumor angiogenesis and vascular abnormality in GBM. Our findings identify SOX4 as a potential vascular therapeutic target to improve drug delivery for GBM treatment.

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来源期刊
CiteScore
8.40
自引率
2.00%
发文量
314
审稿时长
54 days
期刊介绍: Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.
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