Malignant behaviorial characteristics of CD133+/− glioblastoma cells from a Northern Chinese population

摘要

Following emergence of the tumor stem cell theory, the increasing number of related studies demonstrates the theory’s growing importance in cancer research and its potential for clinical applications. Few studies have addressed the in vitro or in vivo properties of glioma stem cells from a Han Chinese population. In the present study, surgically obtained glioblastoma tissue was classified into two subtypes, CD133⁺ and CD133⁻. The hierarchy, invasiveness, growth tolerance under low nutrient conditions and colony forming abilities of the tissue samples were analyzed. Additionally, the characteristics of tumor cells transplanted subcutaneously or re-transplanted into nude mice were observed. The results demonstrated that CD133⁺ glioblastoma cells derived from Han Chinese glioma specimens were more prone to primitive cell differentiation and more invasive than CD133⁻ glioblastoma cells, leading to increased tumor malignancy compared with CD133⁻ cells. The tumor formation rates of CD133⁺ and CD133⁻ cells in mice were 26/30 and 2/30, respectively. A comparison of tumor subtypes demonstrated that CD133⁺ glioblastoma cells had a lower incidence of cell apoptosis in the tumor tissue and higher protein expression levels of Oct4, Sox2, PCNA, EGFR, Ang2, MMP2 and MMP9 compared with CD133⁻ cells. Flow cytometry revealed that in the CD133⁺ and CD133⁻ glioblastoma cell-induced tumors, the percentage of CD133⁺ cells was 2.47±0.67 and 0.44±0.14%, respectively. The tumor formation rates following the re-transplantation of CD133⁺ or CD133⁻ tumors into nude mice were 10/10 and 4/10, respectively. These findings suggest that the CD133⁺ glioblastoma cell subpopulation has a stronger malignant cell phenotype than the CD133⁻ subpopulation and that its recurrence rate is increased compared with the primitive tumorigenic rate following in vivo transplantation.