-
Views
-
Cite
Cite
Suzana Kahn, Ryan Nitta, Kevin Wang, Sharareh Gholamin, Tej Azad, Michael Zhang, Yoon-Jae Cho, Michael Taylor, Siddhartha Mitra, Irving Weissman, Samuel Cheshier, MB-01
NOTCH1 PROMOTES MYC MEDULLOBLASTOMA METASTASIS, INITIATION AND MAINTENANCE, Neuro-Oncology, Volume 17, Issue suppl_3, June 2015, Pages iii19–iii20, https://doi.org/10.1093/neuonc/nov061.77Close - Share Icon Share
Extract
Medulloblastoma (MB) is a malignant brain tumor that originates in the cerebellum in children and spreads via the cerebrospinal fluid to the leptomeningeal spaces of the brain and spinal cord. MB is stratified into four distinct groups, according to genetic and clinical features, and patients from group 3 (also known as c-Myc-amplified) have the highest risk of developing metastatic disease and, consequently, poor prognosis. Treatment protocols involve surgery, craniospinal radiation, and high-dose chemotherapy, which frequently cause disabling neurotoxic effects in long-term survivors. We used MB cell lines and primary cells isolated from patients from the c-Myc-amplified group as tools to understand the cellular determinants of leptomeningeal dissemination. Cells isolated from metastatic tumors express 10 times more NICD1 (Notch1 Intracellular Domain), the active form of Notch1, than cells isolated from primary sites (as quantified by western blot and imunohistochemistry), what implies the upregulation of Notch1 signaling pathway in MB metastasis. Moreover, flow cytometry analyses revealed that the cells isolated from metastatic sites express higher levels of full-length Notch1 when compared to cells from primary sites. These differences occur because of the enrichment in the cancer stem cell population at the metastatic sites, as we observed that MB cells isolated from metastatic tumors exhibit higher self-renewal potential than cells from primary tumor sites.
