Clinical and biological implications of CD133-positive and CD133-negative cells in glioblastomas.
A number of recent reports have demonstrated that only CD133-positive cancer cells of glioblastoma multiforme (GBM) have tumor-initiating potential. These findings raise an attractive hypothesis that GBMs can be cured by eradicating CD133-positive cancer stem cells (CSCs), which are a small portion of GBM cells. However, as GBMs are known to possess various genetic alterations, GBMs might harbor heterogeneous CSCs with different genetic alterations. Here, we compared the clinical characteristics of two GBM patient groups divided according to CD133-positive cell ratios. The CD133-low GBMs showed more invasive growth and gene expression profiles characteristic of mesenchymal or proliferative subtypes, whereas the CD133-high GBMs showed features of cortical and well-demarcated tumors and gene expressions typical of proneuronal subtype. Both CD133-positive and CD133-negative cells purified from four out of six GBM patients produced typical GBM tumor masses in NOD-SCID brains, whereas brain mass from CD133-negative cells showed more proliferative and angiogenic features compared to that from CD133-positive cells. Our results suggest, in contrast to previous reports that only CD133-positive cells of GBMs can initiate tumor formation in vivo CD133-negative cells also possess tumor-initiating potential, which is indicative of complexity in the identification of cancer cells for therapeutic targeting.
Department of Neurosurgery, Samsung Medical Center and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Kyeung Min
KM
Joo
Shi Yean
SY
Kim
Xun
X
Jin
Sang Yong
SY
Song
Doo-Sik
DS
Kong
Jung-Ii
JI
Lee
Ji Won
JW
Jeon
Mi Hyun
MH
Kim
Bong Gu
BG
Kang
Yong
Y
Jung
Juyoun
J
Jin
Seung-Chyul
SC
Hong
Woong-Yang
WY
Park
Dong-Sup
DS
Lee
Hyunggee
H
Kim
Do-Hyun
DH
Nam
D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D019008:Drug Resistance, Neoplasm / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000276:immunology* / Q000473:pathology; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000276:immunology*; D010455:Peptides / Q000378:metabolism*
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse