The Antitumorigenic Response of Neural Precursors Depends on Subventricular Proliferation and Age

Walzlein, Joo Hee; Synowitz, Michael; Engels, Boris; Marković, Darko; Gabrusiewicz, Konrad; Nikolaev, Evgeni; Yoshikawa, Kunio; Kamińska, Bożena; Kempermann, Gerd; Uckert, Wolfgang; Kaczmarek, Leszek; Kettenmann, Helmut; Glaß, Rainer

doi:10.1634/stemcells.2008-0307

Cited by 49 publications

(57 citation statements)

References 40 publications

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“…Large numbers of endogenous NPCs, e.g. from the subventricular zone (SVZ) lining the lateral ventricles or from the corpus callosum, migrate toward experimental brain tumors (Assanah et al, 2006(Assanah et al, , 2009Chirasani et al, 2010;Glass et al, 2005;Walzlein et al, 2008). NPCs home in to pathologic brain tissue and possibly also to tumors due to expression of CXCR4 (Kokovay et al, 2010;Xu et al, 2009).…”

Section: The Interaction Of Glioblastomas With Neural Precursor Cellsmentioning

confidence: 99%

“…with cytochemical markers and by electrophysiology, to be bona fide precursor cells. Viral labeling of proliferative cells in the SVZ of transgenic mice revealed that NPCs accumulate in many cellular layers around gliomas and that the tumor-associated NPCs are diverted from their physiological migratory path to the olfactory bulb (Walzlein et al, 2008).…”

Section: The Interaction Of Glioblastomas With Neural Precursor Cellsmentioning

confidence: 99%

“…Cultivated NPCs release soluble factors that can attenuate glioblastoma proliferation Staflin et al, 2009;Suzuki et al, 2005), cause glioblastoma cell death Walzlein et al, 2008) and induce the differentiation of glioblastoma stem cells (Chirasani et al, 2010). In mouse glioblastoma models, using orthotopic implantation of glioblastoma cells, it was shown that coimplantation of cultivated NPCs improves survival Staflin et al, 2004).…”

Section: The Interaction Of Glioblastomas With Neural Precursor Cellsmentioning

confidence: 99%

“…Adult neurogenesis, describing the presence, proliferation, and differentiation of stem and precursor cells in the adult brain, declines with aging (Kowalczyk et al, 2004;Tropepe et al, 1997). Consequentially, experimental glioblastomas attract large numbers of NPCs only in the young brain, while this effect is strongly reduced in the older brain (Walzlein et al, 2008). The number of glioblastoma-associated NPCs inversely correlates with tumor size and survival.…”

Section: The Interaction Of Glioblastomas With Neural Precursor Cellsmentioning

confidence: 99%

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The brain tumor microenvironment

Charles

Holland

Gilbertson

et al. 2011

Glia

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689

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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Section: The Interaction Of Glioblastomas With Neural Precursor Cellsmentioning

confidence: 99%

Section: The Interaction Of Glioblastomas With Neural Precursor Cellsmentioning

confidence: 99%

Section: The Interaction Of Glioblastomas With Neural Precursor Cellsmentioning

confidence: 99%

Section: The Interaction Of Glioblastomas With Neural Precursor Cellsmentioning

confidence: 99%

See 2 more Smart Citations

The brain tumor microenvironment

Charles

Holland

Gilbertson

et al. 2011

Glia

Self Cite

689

327

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“…We used here the EGFP-expressing mouse cell line GL261 (Walzlein et al, 2008), which is commonly used for the generation of experimental brain tumors in mice. GL261 cells selectively express mRNA coding only for the GlyR a1ins RNA splice variant , and not for a2, a3, a4 or b subunits ( Fig.…”

Section: Characteristics Of Glyr Expression In Mouse Gl261 Glioma Cellsmentioning

confidence: 99%

Intracellular glycine receptor function facilitates glioma formation in vivo

Förstera

Dzaye

Winkelmann

et al. 2014

Journal of Cell Science

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BSTRACTThe neuronal function of Cys-loop neurotransmitter receptors is established; however, their role in non-neuronal cells is poorly defined. As brain tumors are enriched in the neurotransmitter glycine, we studied the expression and function of glycine receptors (GlyRs) in glioma cells. Human brain tumor biopsies selectively expressed the GlyR a1 and a3 subunits, which have nuclear localization signals (NLSs). The mouse glioma cell line GL261 expressed GlyR a1, and knockdown of GlyR a1 protein expression impaired the self-renewal capacity and tumorigenicity of GL261 glioma cells, as shown by a neurosphere assay and GL261 cell inoculation in vivo, respectively. We furthermore showed that the pronounced tumorigenic effect of GlyR a1 relies on a new intracellular signaling function that depends on the NLS region in the large cytosolic loop and impacts on GL261 glioma cell gene regulation. Stable expression of GlyR a1 and a3 loops rescued the self-renewal capacity of GlyR a1 knockdown cells, which demonstrates their functional equivalence. The new intracellular signaling function identified here goes beyond the well-established role of GlyRs as neuronal ligand-gated ion channels and defines NLS-containing GlyRs as new potential targets for brain tumor therapies.

show abstract

The brain tumor microenvironment

Charles

Holland

Gilbertson

et al. 2011

Glia

Self Cite

492

410

View full text Add to dashboard Cite

High-grade brain tumors are heterogeneous with respect to the composition of bona fide tumors 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 and 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 stem and progenitor 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. © 2011 Wiley-Liss, Inc.

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The Antitumorigenic Response of Neural Precursors Depends on Subventricular Proliferation and Age

Cited by 49 publications

References 40 publications

The brain tumor microenvironment

The brain tumor microenvironment

Intracellular glycine receptor function facilitates glioma formation in vivo

The brain tumor microenvironment

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