Membranous expression of glucose transporter-1 protein (GLUT-1) in embryonal neoplasms of the central nervous system.
The human erythrocyte GLUT-1 is a transmembrane protein which facilitates transport of glucose in the cell in an energy-independent fashion. Neuroectodermal stem cells show strong membrane immunoreactivitry with this marker at early developmental stages in rodents. Membranous expression by undifferentiated neuroectodermal cells gradually decreases while GLUT-1 becomes confined to the endothelial cells, when these acquire blood-brain barrier function. We thus sought to determine whether GLUT-1 expression was limited to embryonal neoplasms of the central nervous system (CNS) which are presumably derived from developmentally arrested neuroectodermal stem cells. Archival material of 40 primary CNS neoplasms were examined for immunoreactivity with anti-GLUT-1. This included both non-embryonal neoplasms (18 astrocytic tumours, one ependymoma and three oligodendroglioma) and embryonal neoplasms (12 cerebellar medulloblastomas, four supratentorial PNETs and two atypical teratoid/rhabdoid tumours (AT/RhT)). In addition, cell lines and nude mice xenografts derived from both undifferentiated and differentiated tumours were assessed for GLUT-1 immunoreactivity by both immunohistochemistry and Western blotting. All embryonal tumours, MBs and PNET xenografts consistently showed GLUT-1 membrane staining. Non-embryonal neoplasms were negative except for vascular staining. Membrane protein fraction of embryonal tumours cell lines immunoreacted by immunoblot with GLUT-1, whereas the glioblastoma cell line was negative. Expression of GLUT-1 supports the stem cell nature of the cells of origin of MBs, supratentorial PNET and AT/RhTs. As a result, GLUT-1 is a useful marker to define the embryonal nature of CNS neoplasms.
Loda
M
M
Departments of Adult Oncology, Dana Farber Cancer Institute, Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Xu
X
X
Pession
A
A
Vortmeyer
A
A
Giangaspero
F
F
D000818:Animals; D000906:Antibodies; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D005909:Glioblastoma / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D051272:Glucose Transporter Type 1; D006801:Humans; D008527:Medulloblastoma / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D017599:Neuroectodermal Tumors / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D018335:Rhabdoid Tumor / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000637:transplantation
D000906:Antibodies; D014408:Biomarkers, Tumor; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human; C495678:Slc2a1 protein, mouse