Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Cell. 2018 Feb 22;172(5):1050-1062.e14. doi: 10.1016/j.cell.2018.01.038.
While the preponderance of morbidity and mortality in medulloblastoma patients are due to metastatic disease, most research focuses on the primary tumor due to a dearth of metastatic tissue samples and model systems. Medulloblastoma metastases are found almost exclusively on the leptomeningeal surface of the brain and spinal cord; dissemination is therefore thought to occur through shedding of primary tumor cells into the cerebrospinal fluid followed by distal re-implantation on the leptomeninges. We present evidence for medulloblastoma circulating tumor cells (CTCs) in therapy-naive patients and demonstrate in vivo, through flank xenografting and parabiosis, that medulloblastoma CTCs can spread through the blood to the leptomeningeal space to form leptomeningeal metastases. Medulloblastoma leptomeningeal metastases express high levels of the chemokine CCL2, and expression of CCL2 in medulloblastoma in vivo is sufficient to drive leptomeningeal dissemination. Hematogenous dissemination of medulloblastoma offers a new opportunity to diagnose and treat lethal disseminated medulloblastoma.
尽管髓母细胞瘤患者的大多数发病率和死亡率是由于转移性疾病引起的，但由于转移性组织样本和模型系统的缺乏，大多数研究都集中在原发性肿瘤上。髓母细胞瘤转移几乎只发生在脑和脊髓的软脑膜表面;因此，人们认为播散是通过原发性肿瘤细胞脱落到脑脊液中，然后在软脑膜上再次植入而发生的。我们提出了治疗前患者中存在髓母细胞瘤循环肿瘤细胞（CTC）的证据，并通过侧腹移植和并体实验证明，髓母细胞瘤 CTC 可以通过血液传播到软脑膜间隙形成软脑膜转移。髓母细胞瘤软脑膜转移表达高水平的趋化因子 CCL2，并且 CCL2 在体内表达足以驱动软脑膜播散。髓母细胞瘤的血源性播散为诊断和治疗致命性播散性髓母细胞瘤提供了新的机会。
