Recruited Brain Tumor‐Derived Mesenchymal Stem Cells Contribute to Brain Tumor Progression

Abstract

The identity of the cells that contribute to brain tumor structure and progression remains unclear. Mesenchymal stem cells (MSCs) have recently been isolated from normal mouse brain. Here, we report the infiltration of MSC-like cells into the GL261 murine glioma model. These brain tumor-derived mesenchymal stem cells (BT-MSCs) are defined with the phenotype (LinSca-11CD91CD441CD1661/2) and have multipotent differentiation capacity. We show that the infiltration of BT-MSCs correlates to tumor progression; furthermore, BT-MSCs increased the proliferation rate of GL261 cells in vitro. For the first time, we report that the majority of GL261 cells expressed mesenchymal phenotype under both adherent and sphere culture conditions in vitro and that the non-MSC population is nontumorigenic in vivo. Although the GL261 cell line expressed mesenchymal phenotype markers in vitro, most BT-MSCs are recruited cells from host origin in both wild-type GL261 inoculated into green fluorescent protein (GFP)-transgenic mice and GL261-GFP cells inoculated into wild-type mice. We show the expression of chemokine receptors CXCR4 and CXCR6 on different recruited cell populations. In vivo, the GL261 cells change marker profile and acquire a phenotype that is more similar to cells growing in sphere culture conditions. Finally, we identify a BT-MSC population in human glioblastoma that is CD441CD91CD1661 both in freshly isolated and culture-expanded cells. Our data indicate that cells with MSC-like phenotype infiltrate into the tumor stroma and play an important role in tumor cell growth in vitro and in vivo. Thus, we suggest that targeting BT-MSCs could be a possible strategy for treating glioblastoma patients.

Targeting PBK/TOPK decreases growth and survival of glioma initiating cells in vitro and attenuates tumor growth in vivo

“…Flow cytometry analysis of surface markers was performed as previously described [43]. Intracellular staining was performed by using Fixation/Permeabilization Solution Kit (BD Pharmingen), where cells were incubated with primary antibody over night, followed by washing and then incubated with secondary antibody for 2 h. Cells stained with secondary antibodies alone were used as control for gating.…”

Ultrasonic Surgical Aspirate is a Reliable Source For Culturing Glioblastoma Stem Cells

“…Six to eight-weeks old severe combined immunodeficiency (SCID) mice were purchased from Scanbur (Scanbur AS, Denmark). Sphere cultures were processed into single cells and 100 000 tumor cells in 4 μl neurobasal medium were stereotactically injected as previously described31. Mice were allowed to recover after operations; their health status was closely monitored, and they were immediately euthanized when they started showing neurological symptoms.…”

Potential use of glioblastoma tumorsphere: clinical credentialing

“…These non-tumorigenic cells were named to be glioma associated stem cells (GASC) (Bourkoula et al 2013), tumor associated mesenchymal stromal cells (TAMSC) (Hossain et al 2011), brain tumor derived-mesenchymal stem cell (BTD-MSC) (Behnan et al 2014) and tumor mesenchymal stem like cells (tMSLCs) (Kim et al 2011Kwak et al 2013;Lim et al 2013). It is reported that GASC plays a role to predict the progression of the low grade glioma (Bourkoula et al 2013), BTD-MSC is relevant to tumor progression (Behnan et al 2014) and MSCL is associated with the increase in angiogenesis (Shin et al Fig.…”

“…It is reported that GASC plays a role to predict the progression of the low grade glioma (Bourkoula et al 2013), BTD-MSC is relevant to tumor progression (Behnan et al 2014) and MSCL is associated with the increase in angiogenesis (Shin et al Fig. 1 One example of our GBM TS data set.…”