A distinct subpopulation within CD133 positive brain tumor cells shares characteristics with endothelial progenitor cells.
The cell surface marker CD133 has been proposed as a brain tumor stem cell marker. However, there have been substantial controversies regarding the necessity and role of CD133 in tumorigenesis. This study aimed to characterize CD133(+) cells in brain tumors. Human brain tumor specimens and whole blood were collected from the same patients (N=12). We carried out dual FACS staining for CD133/CD34 and functional tumorigenesis and angiogenesis analyses of CD133(+) cells from different origins. We also investigated the in vivo tumorigenic potential and histological characteristics of four distinct groups on the basis of expression of CD133/CD34 markers (CD133(+), CD133(+)/CD34(+), CD133(+)/CD34(-), and CD133(-)). CD133(+) brain tumor cells coexpressed significantly higher positivity for CD34 (70.7±5.2% in CD133(+) vs. 12.3±4.2% in CD133(-) cells, P<0.001). CD133(+) brain tumor cells formed neurosphere-like spheroids and differentiated into multiple nervous system lineages unlike CD133(+) blood cells. They showed biological characteristics of endothelial cells, including vWF expression, LDL uptake and tube formation in vitro, unlike CD133(-) brain tumors cells. Pathologic analysis of brains implanted with CD133(+) cells showed large, markedly hypervascular tumors with well-demarcated boundary. CD133(+)/CD34(-) cells produced smaller but highly infiltrative tumors. Notably, pure angiogenic cell fractions (CD133(+)/CD34(+)) and CD133(-) tumor cells did not generate tumors in vivo. Our data suggest the presence of a distinct subpopulation of CD133(+) cells isolated from human brain tumors, with characteristics of endothelial progenitor cells (EPCs).
Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, College of Medicine, Seoul, Republic of Korea.
Seung Ah
SA
Choi
Kyu-Chang
KC
Wang
Ji Hoon
JH
Phi
Ji Yeoun
JY
Lee
Chul-Kee
CK
Park
Sung-Hye
SH
Park
Seung-Ki
SK
Kim
D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D018952:Antigens, CD34 / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002469:Cell Separation / Q000379:methods; D002648:Child; D002675:Child, Preschool; D042783:Endothelial Cells / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000276:immunology* / Q000473:pathology; D018919:Neovascularization, Physiologic; D010455:Peptides / Q000378:metabolism*; D010641:Phenotype; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D018874:Spheroids, Cellular; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014841:von Willebrand Factor / Q000378:metabolism
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D006023:Glycoproteins; D008077:Lipoproteins, LDL; C000606023:PROM1 protein, human; D010455:Peptides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C000606024:Prom1 protein, mouse; D014841:von Willebrand Factor