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.

Canada's Michael Smith Genome Sciences Centre BC Cancer Agency and Department of Medical Genetics University of British Columbia Vancouver BC Canada

Department of Immunology University of Toronto Toronto ON Canada

Department of Immunology University of Toronto Toronto ON Canada; Peter Munk Cardiac Centre Toronto General Research Institute University Health Network Toronto ON Canada

Department of Laboratory Medicine and Pathobiology University of Toronto Toronto ON Canada; Toronto General Research Institute University Health Network Toronto ON Canada

Department of Molecular Oncology British Columbia Cancer Research Centre Vancouver BC Canada

Department of Neurosurgery Huntsman Cancer Institute University of Utah Salt Lake City UT USA

Department of Neurosurgery Stanford University School of Medicine Stanford CA USA

Department of Pathology and Laboratory Medicine University of Calgary Calgary AB Canada

Department of Pediatric Hematology and Oncology 2nd Faculty of Medicine University Hospital Motol Charles University Prague Czech Republic

Departments of Pediatrics Neurological Surgery and Neurology University of California San Francisco San Francisco CA USA

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

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; Division of Neurosurgery The Hospital for Sick Children Toronto ON Canada

Division of Haematology Oncology The Hospital for Sick Children Toronto ON Canada; Department of Pediatric Hematology and Oncology 2nd Faculty of Medicine University Hospital Motol Charles University Prague Czech Republic

Division of Hematology Oncology McGill University Montreal QC Canada

Division of Neuro Oncology Massachusetts General Hospital Boston MA USA

Division of Pathology The Hospital for Sick Children Toronto ON Canada

Fondazione IRCCS Istituto Nazionale Tumori Milan Italy

Lunenfeld Tanenbaum Research Institute Mount Sinai Hospital Toronto ON M5G 1X5 Canada

MacFeeters Hamilton Brain Tumour Centre Princess Margaret Cancer Centre University Health Network Toronto ON Canada

The Arthur and Sonia Labatt Brain Tumour Research Centre 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; Division of Haematology Oncology 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; Division of Neurosurgery 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; Division of Pathology The Hospital for Sick Children Toronto ON Canada

Tumor Initiation and Maintenance Program NCI Designated Cancer Center Sanford Burnham Prebys Medical Discovery Institute La Jolla CA USA

Tumor Initiation and Maintenance Program NCI Designated Cancer Center Sanford Burnham Prebys Medical Discovery Institute La Jolla CA USA; Department of Pediatrics University of California San Diego San Diego CA USA

Cancer Discov. 2018 Apr;8(4):383. doi: 10.1158/2159-8290.CD-RW2018-035. PubMed

Cell. 2018 May 31;173(6):1549. doi: 10.1016/j.cell.2018.05.033. PubMed

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