Identification of a cancer stem cell in human brain tumors.
Most current research on human brain tumors is focused on the molecular and cellular analysis of the bulk tumor mass. However, there is overwhelming evidence in some malignancies that the tumor clone is heterogeneous with respect to proliferation and differentiation. In human leukemia, the tumor clone is organized as a hierarchy that originates from rare leukemic stem cells that possess extensive proliferative and self-renewal potential, and are responsible for maintaining the tumor clone. We report here the identification and purification of a cancer stem cell from human brain tumors of different phenotypes that possesses a marked capacity for proliferation, self-renewal, and differentiation. The increased self-renewal capacity of the brain tumor stem cell (BTSC) was highest from the most aggressive clinical samples of medulloblastoma compared with low-grade gliomas. The BTSC was exclusively isolated with the cell fraction expressing the neural stem cell surface marker CD133. These CD133+ cells could differentiate in culture into tumor cells that phenotypically resembled the tumor from the patient. The identification of a BTSC provides a powerful tool to investigate the tumorigenic process in the central nervous system and to develop therapies targeted to the BTSC.
Singh
Sheila K
SK
The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
Clarke
Ian D
ID
Terasaki
Mizuhiko
M
Bonn
Victoria E
VE
Hawkins
Cynthia
C
Squire
Jeremy
J
Dirks
Peter B
PB
D000071916:AC133 Antigen; D000293:Adolescent; D015703:Antigens, CD; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D015192:Infratentorial Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007621:Karyotyping; D008297:Male; D008527:Medulloblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000166:cytology; D010455:Peptides; D010641:Phenotype
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides