Malignant gliomas actively recruit bone marrow stromal cells by secreting angiogenic cytokines

Birnbaum, Tobias; Roider, Julia; Schankin, Christoph; Padovan, Claudio S.; Schichor, Christian; Goldbrunner, Roland; Straube, Andreas

doi:10.1007/s11060-007-9332-4

Cited by 164 publications

(135 citation statements)

References 29 publications

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“…These cells are easy to be obtained from many tissues and can be reprogrammed and expanded efficiently in vitro. However, the caveat for this methodology is that stem cells can be tumorigenic, and this transformation can happen spontaneously, which may cause a worse disease condition (Birnbaum et al, 2007).…”

Section: Other Therapeutic Concerns and Unconventional Potential Thermentioning

confidence: 99%

Neuronal stem cells in the central nervous system and in human diseases

Wang

2012

Protein Cell

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The process of cortical expansion in the central nervous system is a key step of mammalian brain development to ensure its physiological function. Radial glial (RG) cells are a glial cell type contributing to this progress as intermediate neural progenitor cells responsible for an increase in the number of cortical neurons. In this review, we discuss the current understanding of RG cells during neurogenesis and provide further information on the mechanisms of neurodevelopmental diseases and stem cell-related brain tumorigenesis. Knowledge of neuronal stem cell and relative diseases will bridge benchmark research through translational studies to clinical therapeutic treatments of these diseases.

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Section: Other Therapeutic Concerns and Unconventional Potential Thermentioning

confidence: 99%

Neuronal stem cells in the central nervous system and in human diseases

Wang

2012

Protein Cell

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“…and local inflammatory chemokines and cytokines induced by tumor invasion [6,7]. Solid tumor growth and invasion create a microenvironment that induces the secretion of factors that attract MSC to specifically migrate to the tumor sites [8]. This selective tropism for tumor microenvironments gives MSC the ability to selectively deliver growth inhibitory proteins such as interferon-β (IFN-β) and thus render the microenvironment inhospitable to tumor growth.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cells Overexpressing IFN-β Inhibit Breast Cancer Growth and Metastases through Stat3 Signaling in a Syngeneic Tumor Model

Ling

Marini

Konopleva

et al. 2010

Cancer Microenvironment

105

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We previously demonstrated that mesenchymal stem/stromal cells (MSC) are recruited to tumors and that IFN-β produced by MSC inhibited tumor growth in xenograft models. Because of a deficient immune system, murine xenograft models cannot fully recapitulate tumor and immune cell interactions during progression. Therefore we investigated the capacity of MSC to migrate to and engraft into primary breast tumor sites and subsequently explore mechanisms of tumor inhibition by MSC-delivered IFN-β in a syngeneic, immunocompetent murine model. Herein we report that 1) systemically administrated MSC migrate to established 4 T1 breast cancer sites and localize among the tumor-stroma border and throughout the tumor mass; 2) high levels of IFN-β secreted by MSC are detectable in the tumor microenvironment but not in circulation; 3) intratumorally produced IFN-β inactivates constitutive phosphorylation of signal transducer activator transcription factor 3 (Stat3), Src, and Akt and down-regulates cMyc and MMP2 expression in 4 T1 cells, and 4) in mice with established breast cancer IFN-β expressing MSC administered systemically resulted in inhibition of primary cancer growth and in dramatic reduction of pulmonary and hepatic metastases. 5) MSC-IFN-β treated, but not control mice, maintained normal levels of splenic mature dendritic (DC), CD8+ T cells and CD4+/Foxp3+ regulatory T-cells (Treg). Our findings suggest that MSC are capable of migrating to tumor sites in an immunocompetent environment, that IFN-β produced by MSC suppresses breast cancer growth through inhibition of Stat3 signaling, and dramatically reduces pulmonary and hepatic metastases.

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“…For example, plateletderived growth factor-BB, epidermal growth factor and vascular endothelial growth factor-A have all been shown to enhance tumor tropism of MSCs. 10,16 Birnbaum et al 17 reported that the tumor tropism of MSCs is dependent on IL-8, transforming growth factor-b1 and neurotropin-3. In comparison, Xu et al 18 reported that monocyte chemoattractant protein-1 and stromal cell-derived factor-1a have a role in migration of MSCs toward gliomas.…”

Section: Glioma Tropism Of Mscmentioning

confidence: 99%

Therapeutic effect of suicide gene-transferred mesenchymal stem cells in a rat model of glioma

et al. 2012

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We evaluated a new therapeutic strategy for malignant glioma, which combines intratumoral inoculation of mesenchymal stem cells (MSCs) expressing cytosine deaminase gene with 5-fluorocytosine (5-FC) administration. For in vitro and in vivo experiments, MSCs were transfected with adenovirus carrying either enhanced green fluorescent protein gene (AdexCAEGFP) or cytosine deaminase gene (AdexCACD), to establish MSC-expressing EGFP (MSC-EGFP) or CD (MSC-CD). Co-culture of 9L glioma cells with MSC-CD in a medium containing 5-FC resulted in a remarkable reduction in 9L cell viability. The migratory ability of MSC-EGFP toward 9L cells was demonstrated by double-chamber assay. For the in vivo study, rats harboring 9L brain tumors were inoculated with MSC-EGFP or MSC-CD. Immunohistochemistry of rat brain tumors inoculated with MSC-EGFP showed intratumoral distribution of MSC-EGFP. Survival analysis of rats bearing 9L gliomas treated with intratumoral MSC-CD and intraperitoneal 5-FC resulted in significant prolongation of survival compared with control animals. In conclusion, molecular therapy combining suicide gene therapy and MSCs as a targeting vehicle represents a potential new therapeutic approach for malignant glioma, both with respect to the antitumor potential of this system and its neuroprotective effect on normal brain tissue.

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Malignant gliomas actively recruit bone marrow stromal cells by secreting angiogenic cytokines

Cited by 164 publications

References 29 publications

Neuronal stem cells in the central nervous system and in human diseases

Neuronal stem cells in the central nervous system and in human diseases

Mesenchymal Stem Cells Overexpressing IFN-β Inhibit Breast Cancer Growth and Metastases through Stat3 Signaling in a Syngeneic Tumor Model

Therapeutic effect of suicide gene-transferred mesenchymal stem cells in a rat model of glioma

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