文章：

胶质瘤干细胞样细胞中钙三醇信号传导与敏感性的分子决定因素

Molecular Determinants of Calcitriol Signaling and Sensitivity in Glioma Stem-like Cells

原文发布日期：31 October 2023

DOI: 10.3390/cancers15215249

类型: Article

开放获取: 是

英文摘要：

Glioblastoma is the most common primary brain cancer in adults and represents one of the worst cancer diagnoses for patients. Suffering from a poor prognosis and limited treatment options, tumor recurrences are virtually inevitable. Additionally, treatment resistance is very common for this disease and worsens the prognosis. These and other factors are hypothesized to be largely due to the fact that glioblastoma cells are known to be able to obtain stem-like traits, thereby driving these phenotypes. Recently, we have shown that the in vitro and ex vivo treatment of glioblastoma stem-like cells with the hormonally active form of vitamin D3, calcitriol (1α,25(OH)2-vitamin D3) can block stemness in a subset of cell lines and reduce tumor growth. Here, we expanded our cell panel to over 40 different cultures and can show that, while half of the tested cell lines are sensitive, a quarter can be classified as high responders. Using genetic and proteomic analysis, we further determined that treatment success can be partially explained by specific polymorphism of the vitamin D3receptor and that high responders display a proteome suggestive of blockade of stemness, as well as migratory potential.

摘要翻译： 

胶质母细胞瘤是成人中最常见的原发性脑癌，也是患者预后最差的癌症诊断之一。由于预后不良且治疗选择有限，肿瘤复发几乎不可避免。此外，该疾病普遍存在治疗抵抗现象，进一步恶化了预后。这些及其他因素被认为主要源于胶质母细胞瘤细胞能够获得类干细胞特性，从而驱动这些表型。近期研究发现，使用维生素D3的激素活性形式——骨化三醇（1α,25(OH)2-维生素D3）对胶质母细胞瘤干细胞样细胞进行体外和离体处理，能够阻断部分细胞系的干细胞特性并抑制肿瘤生长。本研究将细胞样本库扩展至40余种不同培养体系，结果显示半数受试细胞系对治疗敏感，其中四分之一可归类为高应答型。通过遗传学和蛋白质组学分析进一步发现，治疗成效部分可由维生素D3受体的特异性多态性解释，且高应答型细胞展现出提示干细胞特性阻断及迁移潜能抑制的蛋白质组特征。

原文链接：

Molecular Determinants of Calcitriol Signaling and Sensitivity in Glioma Stem-like Cells