Microglia function in brain tumors

Watters, Jyoti J.; Schartner, Jill; Badie, Behnam

doi:10.1002/jnr.20485

Cited by 305 publications

(269 citation statements)

References 90 publications

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“…The majority of these cells are tumor-associated macrophages (Ghosh Anirban, 2010;Graeber et al, 2002;Watters et al, 2005). Resident macrophages of the brain are termed microglia.…”

Section: Microglia/macrophages Accumulate Within and Around Gliomasmentioning

confidence: 99%

The brain tumor microenvironment

Charles

Holland

Gilbertson

et al. 2011

Glia

693

327

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High-grade brain tumors are heterogeneous with respect to the composition of bona fide tumor cells and with respect to a range of intermingling parenchymal cells. Glioblastomas harbor multiple cell types, some with increased tumorigenicity and stem cell-like capacity. The stem-like cells may be the cells of origin for tumor relapse. However, the tumor-associated parenchymal cells such as vascular cells, microglia, peripheral immune cells, and neural precursor cells also play a vital role in controlling the course of pathology. In this review, we describe the multiple interactions of bulk glioma cells and glioma stem cells with parenchymal cell populations and highlight the pathological impact as well as signaling pathways known for these types of cell-cell communication. The tumor-vasculature not only nourishes glioblastomas, but also provides a specialized niche for these stem-like cells. In addition, microglial cells, which can contribute up to 30% of a brain tumor mass, play a role in glioblastoma cell invasion. Moreover, non-neoplastic astrocytes can be converted into a reactive phenotype by the glioma microenvironment and can then secrete a number of factors which influences tumor biology. The young brain may have the capacity to inhibit gliomagenesis by the endogenous neural precursor cells, which secrete tumor suppressive factors. The factors, pathways, and interactions described in this review provide a new prospective on the cell biology of primary brain tumors, which may ultimately generate new treatment modalities. However, our picture of the multiple interactions between parenchymal and tumor cells is still incomplete. V

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“…The majority of these cells are tumor-associated macrophages (Ghosh Anirban, 2010;Graeber et al, 2002;Watters et al, 2005). Resident macrophages of the brain are termed microglia.…”

Section: Microglia/macrophages Accumulate Within and Around Gliomasmentioning

confidence: 99%

The brain tumor microenvironment

Charles

Holland

Gilbertson

et al. 2011

Glia

693

327

View full text Add to dashboard Cite

show abstract

“…Microglia can be stained as CD11b þ CD45 low and infiltrating macrophages as CD11b þ CD45 hi (ref. 59). This approach cannot compare the difference between the primary core and infiltrating tumor but our study does indicate that particular subtypes of TAMs may be more important for glioma invasiveness and that this requires an interaction with SDF-1 signaling pathways.…”

Section: Sdf-1 Promotes Glioma Invasion and Tam Tropism S-c Wang Et Almentioning

confidence: 99%

Tumor-secreted SDF-1 promotes glioma invasiveness and TAM tropism toward hypoxia in a murine astrocytoma model

Wang

Hong

Hsueh

et al. 2012

Laboratory Investigation

157

143

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A distinguishing feature of high-grade gliomas is the infiltration of neoplastic cells into adjacent brain tissues that mark most of these tumors surgically incurable. To study the factors associated with tumor invasion, we established a new murine brain tumor model, ALTS1C1 derived from SV40 large T antigen-transfected astrocytes. This new brain tumor model recapitulates several histopathological features of human high-grade glioma including increased cellularity, prominent cellular pleomorphism, geographic necrosis, active mitosis, and extensive invasion of tumor cells into adjacent brain tissues. More importantly, ALTS1C1 expressed a relatively high level of stromal-derived factor-1 (SDF-1/CXCL12) in vitro and in vivo and higher microvascular density (MVD) in vivo. To define the roles of SDF-1 in this tumor model, the expression of SDF-1 in ALTS1C1 cells was inhibited by specific siRNA. SDF-knockdown ALTS1C1 (SDF kd ) cells took longer than parental ALTS1C1 cells to form tumors and in contrast to the wild-type tumors they had well-defined regular borders and lacked infiltration tracts. The SDF kd tumors were also associated with a lower MVD and more hypoxic areas. In contrast to parental tumors, the density of F4/80-positive tumor-associated macrophages (TAMs) in SDF kd tumor was higher in non-hypoxic than in hypoxic regions. SDF-1 production by tumor cells therefore seems critical for the aggregation of TAMs into areas of hypoxia and tumor invasiveness. This study not only provides new insight into the role of SDF-1 in brain tumor invasion and the relationship between TAMs and hypoxia, but also provides a new preclinical brain tumor model for designing new treatment options for invasive cases.

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“…In anaplastic astrocytomas and glioblastomas, microglia contribute significantly to the total tumour mass but the fact that neoplastic cells manage to survive and grow in their presence indicate the failure of normal defence mechanisms [5,6]. The causes of poor microglial response to tumour cells are still unclear although recent studies have demonstrated glioma-infiltrating microglial cells show an impairment of antigen presenting functions [6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

The lack of expression of the peripheral benzodiazepine receptor characterises microglial response in anaplastic astrocytomas

et al. 2007

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The peripheral benzodiazepine receptor (PBR) is a 18 kDa molecule mainly involved in cholesterol transport through the mitochondrial membrane. In microglia, PBR is expressed from the earliest stages of activation and appears to exert a pro-inflammatory function. This molecule is commonly up-regulated in inflammatory, degenerative, infective and ischaemic lesions of the central nervous system but it has never been reported in glioma-infiltrating microglia. We examined two anaplastic astrocytomas showing minimal contrast-enhancement and therefore little damage of the blood brain barrier to minimise the presence of blood borne macrophages within tumour tissue. The two lesions were studied in vivo using positron emission tomography (PET) with the specific PBR ligand [ 11 C](R)-PK11195 and the corresponding tumour tissue was investigated with an anti-PBR antibody. Glioma-infiltrating microglia were characterised for molecules involved in antigen presentation and cytotoxic activity. As comparison, PBR was investigated in three brains with multiple sclerosis (MS) and three with Parkinson's disease (PD). The expression profile of four anaplastic astrocytomas was also exploited and results were compared to the profile of eleven samples of normal temporal lobe and nine cases of PD. PET studies showed that [ 11 C](R)-PK11195 binding was markedly lower in tumours than in the contralateral grey matter. Pathological investigation revealed that glioma-infiltrating microglia failed to express PBR and cytotoxic molecules although some cells still expressed antigen presenting molecules. PBR and cytotoxic molecules were highly represented in MS and PD. Evaluation of microarray datasets confirmed these differences. Our results demonstrated PBR suppression in glioma-infiltrating microglia and suggested that PBR may have a relevant role in modulating the anti-tumour inflammatory response in astrocytic tumours.

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Microglia function in brain tumors

Cited by 305 publications

References 90 publications

The brain tumor microenvironment

The brain tumor microenvironment

Tumor-secreted SDF-1 promotes glioma invasiveness and TAM tropism toward hypoxia in a murine astrocytoma model

The lack of expression of the peripheral benzodiazepine receptor characterises microglial response in anaplastic astrocytomas

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