Neural Progenitor Cell Lines Inhibit Rat Tumor Growth <b>
                     <i>in Vivo</i>
                  </b>

Staflin, Karin; Honeth, Gabriella; Kalliomäki, Suzanne; Kjellman, Christian; Edvardsen, Klaus; Lindvall, Magnus

doi:10.1158/0008-5472.can-03-1246

Cited by 79 publications

(69 citation statements)

References 34 publications

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“…The abundance of neural precursors at the tumor is associated with reduced tumor size and increased survival as studied in an animal model, and in vitro, precursor cells have a direct antitumorigenic effect. Such antitumorigenic effects have been described previously for exogenously added immortalized neural precursor cells from newborn mice (Benedetti et al, 2000;Staflin et al, 2004), but in those studies, no relationship to endogenous, nonimmortalized precursor cells could be established. Implanted immortalized precursors display tropism for experimental glioblastomas (Aboody et al, 2000).…”

Section: Discussionmentioning

confidence: 79%

“…Interestingly, however, the unmodified control cells in that study enhanced survival, too. A recent study confirmed the effects on survival of in vitro expanded neural precursor cell lines administered into gliomas (Staflin et al, 2004). Currently, no gene therapy strategies have been approved for glioblastoma, and clinicians rely on the classic therapies, namely, surgery, chemotherapy, and cranial irradiation (Noble, 2000).…”

Section: Introductionmentioning

confidence: 91%

See 1 more Smart Citation

Glioblastoma-Induced Attraction of Endogenous Neural Precursor Cells Is Associated with Improved Survival

Glaß

Synowitz²,

Kronenberg³

et al. 2005

J. Neurosci.

192

172

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Neural precursor cells contribute to adult neurogenesis and to limited attempts of brain repair after injury. Here we report that in a murine experimental glioblastoma model, endogenous neural precursors migrate from the subventricular zone toward the tumor and surround it. The association of endogenous precursors with syngenic tumor grafts was observed, after injecting red fluorescent proteinlabeled G261 cells into the caudate-putamen of transgenic mice, which express green fluorescent protein under a promoter for nestin (nestin-GFP). Fourteen days after inoculation, the nestin-GFP cells surrounded the tumors in several cell layers and expressed markers of early noncommitted and committed precursors. Nestin-GFP cells were further identified by a characteristic membrane current pattern as recorded in acute brain slices. 5-Bromo-2-deoxyuridine labeling and dye tracing experiments revealed that the tumor-associated precursors originated from the subventricular zone. Moreover, in cultured explants from the subventricular zone, the neural precursors showed extensive tropism for glioblastomas. Tumor-induced endogenous precursor cell accumulation decreased with age of the recipient; this correlated with increased tumor size and shorter survival times in aged mice. Coinjection of glioblastoma cells with neural precursors improved the survival time of old mice to a level similar to that in young mice. Coculture experiments showed that neural precursors suppressed the rapid increase in tumor cell number, which is characteristic of glioblastoma, and induced glioblastoma cell apoptosis. Our results indicate that tumor cells attract endogenous precursor cells; the presence of precursor cells is antitumorigenic; and this cellular interaction decreases with aging.

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Section: Discussionmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 91%

Glioblastoma-Induced Attraction of Endogenous Neural Precursor Cells Is Associated with Improved Survival

Glaß

Synowitz²,

Kronenberg³

et al. 2005

J. Neurosci.

192

172

View full text Add to dashboard Cite

show abstract

“…Benedetti and Staflin et al described the ability of nonengineered rat neural progenitors to inhibit glioma growth in vivo. 25,26 The exact mechanism underlying the observations remains unclear, although they have reported that NSCs may elaborate a secretory agent that could inhibit tumor cell growth. For verifying this demonstration, we co-cultured BMSCs and C6 at the ratio of 1:1.…”

Section: Discussionmentioning

confidence: 99%

The anti-glioma effect of suicide gene therapy using BMSC expressing HSV/TK combined with overexpression of Cx43 in glioma cells

Huang

Xz²,

et al. 2009

Cancer Gene Ther

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The disseminated neoplastic foci of malignant gliomas are essentially responsible for the limited efficacy of current available therapeutic modalities. Bone marrow-derived stem cells (BMSCs) have the ability to migrate into these tumors and even track infiltrating tumor cells, making them to be promising cellular vehicles for delivering therapeutic agents to glioma cells. The herpes simplex virus thymidine kinase (HSV-TK)/ganciclovir (GCV) suicide gene therapy with a potent bystander effect has been considered as one of the most promising therapeutic strategies for malignant gliomas. In this study, we evaluate the anti-glioma effect of suicide gene therapy using BMSCs expressing HSV-TK combined with overexpression of connexin 43 (Cx43), which can restore the gap junction of intercellular communication and may enhance the bystander effect of suicide gene therapy. To assess the potential of BMSCs to track glioma cells, a spheroid co-culture system in matrigel was used to show that some BMSCs migrated to C6 glioma cell microspheres. Transwell assay showed the tumor tropic property of BMSCs. In addition, BrdU-labeled BMSCs injected directly into the cerebral hemisphere opposite to the established C6 rat gliomas were capable of migrating into the xenograft gliomas. C6 cell growth was more intensively inhibited by HSV-TK/GCV treatment mediated by BMSCs, and could be further enhanced by combination with Cx43 transfection into glioma cells. The same result was observed in vivo by the growth of C6 gliomas and the survival analysis of rats bearing C6 glioma. In conclusion, Cx43 combined with HSV-TK/GCV gene therapy using BMSCs as vehicles was highly effective in a rat glioma model and therefore hold great potential as a novel approach for the gene therapy of human malignant gliomas.

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“…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). The tumor-suppressing capacity of endogenous NPCs may explain, why glioma growth is attenuated in younger animals and why younger mice outlive older animals after glioblastoma inoculation into the brain.…”

Section: The Interaction Of Glioblastomas With Neural Precursor Cellsmentioning

confidence: 99%

The brain tumor microenvironment

Charles

Holland

Gilbertson

et al. 2011

Glia

687

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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Neural Progenitor Cell Lines Inhibit Rat Tumor Growth in Vivo

Abstract: ABSTRACT

Cited by 79 publications

References 34 publications

Glioblastoma-Induced Attraction of Endogenous Neural Precursor Cells Is Associated with Improved Survival

Glioblastoma-Induced Attraction of Endogenous Neural Precursor Cells Is Associated with Improved Survival

The anti-glioma effect of suicide gene therapy using BMSC expressing HSV/TK combined with overexpression of Cx43 in glioma cells

The brain tumor microenvironment

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