Cancer Stem Cells Are Enriched in the Side Population Cells in a Mouse Model of Glioma

Abstract

The recent identification of cancer stem cells (CSCs) in multiple human cancers provides a new inroad to understanding tumorigenesis at the cellular level. CSCs are defined by their characteristics of self-renewal, multipotentiality, and tumor initiation upon transplantation. By testing for these defining characteristics, we provide evidence for the existence of CSCs in a transgenic mouse model of glioma, S100b-verbB;Trp53. In this glioma model, CSCs are enriched in the side population (SP) cells. These SP cells have enhanced tumor-initiating capacity, self-renewal, and multipotentiality compared with non-SP cells from the same tumors. Furthermore, gene expression analysis comparing fluorescence-activated cell sorting-sorted cancer SP cells to non-SP cancer cells and normal neural SP cells identified 45 candidate genes that are differentially expressed in glioma stem cells. We validated the expression of two genes from this list (S100a4 and S100a6) in primary mouse gliomas and human glioma samples. Analyses of xenografted human glioblastoma multiforme cell lines and primary human glioma tissues show that S100A4 and S100A6 are expressed in a small subset of cancer cells and that their abundance is positively correlated to tumor grade. In conclusion, this study shows that CSCs exist in a mouse glioma model, suggesting that this model can be used to study the molecular and cellular characteristics of CSCs in vivo and to further test the CSC hypothesis. [Cancer Res 2008;68(24):10051-9]

The intrinsic fusogenicity of glioma cells as a factor of transformation and progression in the tumor microenvironment

“…Although many cell lines established from high-grade gliomas, including U87MG, exhibit mesenchymal characteristics, it is significant that the recombination with fibroblasts reinforced the migratory capacity of the cells. Furthermore, the cells formed by fibroblast/glioma cell recombination displayed high level of expression of the calcium-binding protein S100A4, whose abundance in human brain tumor tissue is correlated to tumor grade; 31 interestingly, heterotypic fusion is consistent with the finding of the S100A4-expressing glioma cells in a perivascular localization. The preservation of functional underpinnings for proliferation after tumor recombination despite acquisition of aneuploidy, provides a solid mechanistic basis for nontransformed cells of the tumor microenvironment to directly contribute to the mesenchymal drift of gliomas.…”

Ovarian cancer stem-like side-population cells are tumourigenic and chemoresistant

“…Our study indicates that ovarian cancer cells are heterogeneous. SP cells are highly proliferative compared with non-SP cells; SP xenogeneic transplant mice grew more tumours than non-SP xenogeneic transplant mice, as shown from other studies (Chiba et al, 2008;Harris et al, 2008;Steiniger et al, 2008). SP cells have characteristics of cancer stem-like cells.…”

Hyaluronic Acid Mediated Enrichment of CD44 Expressing Glioblastoma Stem Cells in U251MG Xenograft Mouse Model

“…Similar studies have been conducted in breast and colon cancer previously [23,24] along with combining the genetic model with xenograft transplantations [25]. Similar studies has shown that the CD133+ conditioned media in glioma enhances the angiogenesis in patient xenografts in mouse by elevated VEGF expression and endothelial differentiation thereby the presence of stem cell populations determines the key events in angiogenesis and vascular mimicry [26][27][28].…”