The molecular profile of microglia under the influence of glioma

Abstract

Microglia, which contribute substantially to the tumor mass of glioblastoma, have been shown to play an important role in glioma growth and invasion. While a large number of experimental studies on functional attributes of microglia in glioma provide evidence for their tumor-supporting roles, there also exist hints in support of their anti-tumor properties. Microglial activities during glioma progression seem multifaceted. They have been attributed to the receptors expressed on the microglia surface, to glioma-derived molecules that have an effect on microglia, and to the molecules released by microglia in response to their environment under glioma control, which can have autocrine effects. In this paper, the microglia and glioma literature is reviewed. We provide a synopsis of the molecular profile of microglia under the influence of glioma in order to help establish a rational basis for their potential therapeutic use. The ability of microglia precursors to cross the blood-brain barrier makes them an attractive target for the development of novel cell-based treatments of malignant glioma.

Glioblastoma cells induce differential glutamatergic gene expressions in human tumor-associated microglia/macrophages and monocyte-derived macrophages

“…8 For example, analysis of TAMs in a murine glioma model has reported the acquisition of the alternative, pro-tumor phenotype of TAMs in the course of tumor development. 11 Moreover, a study has shown that a 48-hour incubation with glioma cells triggered an alternative, tumor-promoting profile in human monocytes.…”

“…Analyses of surgically resected glioblastoma tissues show that as much as 30% of the tissue consisted of tumorassociated microglia/macrophages (TAMs), 5,6 which are derived from parenchymal microglia in the brain and monocytes-derived macrophages from the blood. 7,8 These analyses moreover show that the number of TAMs in the tumor region correlated with the histological grade of gliomas. 9,10 TAMs in the presence of glioma cells become immunosuppressive and elicit an anti-inflammatory response by increasing the expression and release of cytokines such as IL-10 and VEGF, thereby contributing to a milieu that promotes the survival and growth of the glioblastoma cells.…”

“…9,10 TAMs in the presence of glioma cells become immunosuppressive and elicit an anti-inflammatory response by increasing the expression and release of cytokines such as IL-10 and VEGF, thereby contributing to a milieu that promotes the survival and growth of the glioblastoma cells. 8,11,12 Microglia express functional glutamate receptors, 13,14 and microglia as well as macrophages are capable of inducing expression of glutamate transporters and glutamine synthetase in neuropathological conditions, 15 suggesting a functional role of microglia and macrophages in glutamate signaling. However, little is known about the role of TAMs in response to the dysregulation of glutamate signaling in a glioblastoma microenvironment.…”

Probing the Bi-directional Interaction Between Microglia and Gliomas in a Tumor Microenvironment on a Microdevice

“…Since then, numerous studies have shown that microglia are found in high-grade malignant gliomas and form the major components of glioma-infiltrating cells [8]. Some studies have indicated that microglia play an immune defensive effect against glioma and inhibit the proliferation and growth of glioma [25].…”

“…the issue of whether microglia suppress or enhance glioma growth remains controversial. Compelling evidence has shown that glioma cells could suppress the immune surveillance functions of microglia [8,9] and respond to their products by increasing proliferation or invasion [10]. There also exist hints in support of gliomacytotoxic effects of microglia [11,12].…”