gms | German Medical Science

Objective: Microglia cells represent the immune system of the mammalian brain and constitute up to one third of the brain tumor compartment. Nevertheless, the role of microglia in glioblastoma has remained unclear. The aim of our research is to investigate the microglia-tumor-interaction, especially the role of microglia on tumor angiogenesis.

Methods: First, we have studied the phenotype and contribution of microglia cells in the tumor area. Therefore, we implanted intracranially GL261 tumor cells into syngeneic mice. The analysis was performed by immunofluorescence staining in sections from these brains. Second, we purified microglia cells of naïve and tumor bearing mice by MACS technology. These isolated cells were used for RNA extraction following Realtime-PCR of pro-angiogenic factors. In addition, the microglia cells were cultivated in vitro and immunostained to determine their phenotype

Results: We found an increased number of microglia cells in the tumor area, expressing Iba-1, CD11b and CD68. These Iba-1⁺ cells showed a preference for the perivascular niche particularly in the tumor rim, the region with the highest angiogenic activity. Furthermore, we isolated CD11b⁺ cells from mice brains with a purity of more than 93%. The expression analysis of these cells from tumor bearing mice showed an upregulation of pro-angiogenic factors (e.g. angptl6, stc1, flt1). Moreover, we could mimic the situation of microglia in the tumor area by cultivating microglia cells with tumor-conditioned medium in vitro. In this case, stimulated microglia displayed an activated phenotype in contrast to naïve cells.

Conclusions: Our study suggests that the intrinsic immune system of the CNS is involved in tumor angiogenesis in malignant glioma. According to our model tumor cells activate microglia cells, which then localize to the perivascular niche and stimulate blood vessel growth.