Molecular characteristics of cancer stem cells and progenitors in medulloblastoma
Magdalena Zakrzewska, Paweł P. Liberski
Medulloblastoma is the most common type of embryonal tumours in paediatric population. Recently, on the basis of modern molecular analyses comprising gene expression profiling several molecular subtypes of that tumour were described. One of the conclusions from such studies is plausible different cellular origin of medulloblastoma with various molecular profiles. Up to now two main origins of precursors were proposed for this type of tumour, external granule layer (EGL) and cerebellar ventricular zone (CVZ). Recently other structures containing such cells (white matter of the cerebellum, rhombic lip, Bergmann glia) were also identified. Neural stem cells and/or progenitors existing within those regions have capacity to self-renew, multilineage differentiation and tendency to neurosphere formation. Molecular alterations of precursor cells can transform them into tumour stem cells (TSC). TSC, like normal stem cells frequently expresses CD133 protein, what was observed also in medulloblastoma. Moreover, CD133-negative cells without neurosphere- like formation were also detected. Expression of ATOH1 gene was proposed for identification of this type of cells. Among other markers of TSC in medulloblastoma, expression of FUT4, CXCR4, NGFR, CALB1, OTX2, SOX2 and SOX9 genes was mentioned. Proper identification of tumour stem cells and progenitor cells in this high grade tumour may become useful for individualizing of the therapy in children with medulloblastoma.