美国圣路易斯华盛顿大学Erik D. Herzog团队近期取得重要工作进展，他们研究提出，每日使用糖皮质激素可促进胶质母细胞瘤的生长，和宿主的昼夜节律同步。相关研究成果2024年12月12日在线发表于《癌细胞》杂志上。

据介绍，胶质母细胞瘤（GBM）是成人最常见的原发性恶性脑肿瘤，尽管进行了积极的治疗，但预后不良。

研究人员假设日常宿主信号调节肿瘤生长并同步GBM的昼夜节律。研究人员发现日常糖皮质激素通过糖皮质激素受体（GR）信号促进或抑制GBM生长，这取决于一天中的时间和时钟基因Bmal1和Cry。阻断昼夜节律信号，如血管活性肠肽或糖皮质激素，会显著减缓GBM的生长和疾病进展。

对来自癌症基因组图谱（TCGA）的人类GBM样本的分析表明，高GR表达显著增加了死亡风险。最后，无论肿瘤类型或宿主免疫状态如何，小鼠和人类GBM模型在体外和体内的时钟基因表达中都有内在的昼夜节律，通过糖皮质激素信号传导给宿主。

总之，研究人员提出，GBM与大脑的昼夜节律回路有关，通过时钟控制的线索（如糖皮质激素）调节其生长。

附：英文原文

Title: Daily glucocorticoids promote glioblastoma growth and circadian synchrony to the host

Author: Maria F. Gonzalez-Aponte, Anna R. Damato, Tatiana Simon, Nigina Aripova, Fabrizio Darby, Myung Sik Jeon, Jingqin Luo, Joshua B. Rubin, Erik D. Herzog

Issue&Volume: 2024-12-12

Abstract: Glioblastoma (GBM) is the most common primary malignant brain tumor in adults with a poor prognosis despite aggressive therapy. Here, we hypothesized that daily host signaling regulates tumor growth and synchronizes circadian rhythms in GBM. We find daily glucocorticoids promote or suppress GBM growth through glucocorticoid receptor (GR) signaling depending on time of day and the clock genes, Bmal1 and Cry. Blocking circadian signals, like vasoactive intestinal peptide or glucocorticoids, dramatically slows GBM growth and disease progression. Analysis of human GBM samples from The Cancer Genome Atlas (TCGA) shows that high GR expression significantly increases hazard of mortality. Finally, mouse and human GBM models have intrinsic circadian rhythms in clock gene expression in vitro and in vivo that entrain to the host through glucocorticoid signaling, regardless of tumor type or host immune status. We conclude that GBM entrains to the circadian circuit of the brain, modulating its growth through clock-controlled cues, like glucocorticoids.

DOI: 10.1016/j.ccell.2024.11.012

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(24)00447-1