近日，加拿大病童医院教授Michael D. Taylor及其研究组揭示了转移性髓母细胞瘤重塑局部小脑膜微环境，促进进一步转移定植和生长。2025年4月22日出版的《自然—细胞生物学》发表了这项成果。

本研究表明，转移相关的脑膜成纤维细胞（MB-MAFs）在转录上是独特的，并广泛地向肿瘤细胞和肿瘤微环境发出信号。转移细胞分泌血小板衍生生长因子（PDGF）配体进入局部微环境，以化学方式招募脑膜成纤维细胞。脑膜成纤维细胞被重新编程为MB-MAFs，表达不同的转录组和分泌组，包括骨形态发生蛋白。活跃的骨形态发生蛋白信号传导和肿瘤细胞与MB-MAFs的共植入增强了成神经管细胞瘤细胞对轻脑膜的定植，促进了已建立的转移瘤的生长。

此外，用PDGF受体-α中和抗体治疗患者来源的异种移植小鼠可提高体内总存活率。总的来说，他们的结果确定了转移性生态位中可靶向的细胞间通讯级联，以治疗轻脑膜病。

研究人员表示，轻脑膜转移是髓母细胞瘤患者发病率和死亡率的主要原因。脑膜轻脑膜转移的生物学和局部肿瘤微环境的特征尚不清楚。

附：英文原文

Title: Metastatic medulloblastoma remodels the local leptomeningeal microenvironment to promote further metastatic colonization and growth

Author: Abeysundara, Namal, Rasnitsyn, Alexandra, Fong, Vernon, Bahcheli, Alexander, Van Ommeren, Randy, Juraschka, Kyle, Vladoiu, Maria, Ong, Winnie, Livingston, Bryn, de Antonellis, Pasqualino, Ly, Michelle, Holgado, Borja Lpez, Sirbu, Olga, Bahrampour, Shahrzad, Min, Hyun-Kee, Fan, Jerry, Nor, Carolina, Visvanathan, Abhirami, Zhang, Jiao, Wang, Hao, Qin, Lei, Huang, Ning, Pallotta, Jonelle, Douglas, Tajana, Mak, Esta, Su, Haipeng, Ng, Karen, Zhang, Kevin Yang, Daniels, Craig, Lucas, Calixto-Hope G., Eberhart, Charles G., Liu, Hailong, Jiang, Tao, Notta, Faiyaz, Ramaswamy, Vijay, Reimand, Jri, Gallo, Marco, Rich, Jeremy N., Wu, Xiaochong, Huang, Xi, Taylor, Michael D.

Issue&Volume: 2025-04-22

Abstract: Leptomeningeal metastases are the major source of morbidity and mortality for patients with medulloblastoma. The biology of the leptomeningeal metastases and the local tumour microenvironment are poorly characterized. Here we show that metastasis-associated meningeal fibroblasts (MB-MAFs) are transcriptionally distinct and signal extensively to tumour cells and the tumour microenvironment. Metastatic cells secrete platelet-derived growth factor (PDGF) ligands into the local microenvironment to chemotactically recruit meningeal fibroblasts. Meningeal fibroblasts are reprogrammed to become MB-MAFs, expressing distinct transcriptomes and secretomes, including bone morphogenetic proteins. Active bone morphogenetic protein signalling and co-implantation of tumour cells with MB-MAFs enhances the colonization of the leptomeninges by medulloblastoma cells and promotes the growth of established metastases. Furthermore, treatment of patient-derived xenograft mice with a PDGF-receptor-α neutralizing antibody enhances overall survival in vivo. Collectively, our results define a targetable intercellular communication cascade in the metastatic niche to treat leptomeningeal disease.

DOI: 10.1038/s41556-025-01660-7

Source: https://www.nature.com/articles/s41556-025-01660-7