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).