Vascular endothelial growth factor A contributes to glioma-induced migration of human marrow stromal cells (hMSC)

Schichor, Christian; Birnbaum, Tobias; Etminan, Nima; Schnell, Oliver; Grau, Stefan; Miebach, Sabine; Aboody, Karen S.; Padovan, Claudio S.; Straube, Andreas; Tonn, Jörg‐Christian; Goldbrunner, Roland

doi:10.1016/j.expneurol.2005.11.027

Cited by 125 publications

(100 citation statements)

References 26 publications

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“…Accordingly, BMSC migration capacity and their chemotactic response to circulating tumor-derived growth factors has led to the demonstration that BMSC can efficiently migrate toward experimental gliomas, making these cells a promising candidate for cellular carrier systems of anti-glioma therapy (41,42). Among the circulating chemotactic mediators, chemokines play key roles in hematopoietic stem cell trafficking (43), while circulating lipid mediators such as S1P have emerged as one of the most potent in vitro BMSC chemotactic agents (13,14).…”

Section: Discussionmentioning

confidence: 99%

MT1-MMP Down-regulates the Glucose 6-Phosphate Transporter Expression in Marrow Stromal Cells

Currie¹,

Fortier²,

Sina³

et al. 2007

Journal of Biological Chemistry

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Recent advances in the understanding of stem cell mobilization, cell-matrix interaction, and biodistribution have enabled the development of new therapeutic strategies (1, 2). Although locally transplanted bone marrow-derived stromal cells (BMSC) 2 have already been used clinically (3-5), less invasive routes of BMSC transplantation have become the focus of recent attention (6 -8). In fact, several clinical applications now use intravenous administration of genetically engineered BMSC either as an ideal vehicle for gene transfer or as a platform for the systemic delivery of therapeutic recombinant proteins in vivo (6,9,10). This implies that these circulating, systemically infused cells must respond to serum-derived cues that direct their ultimate biodistribution. The molecular players regulating cellular mobilization, chemotaxis, and cell survival of BMSC have received little attention.Among the mediators known to exert potent cellular chemotactic effects, sphingosine 1-phosphate (S1P) is one of the most important bioactive lysophospholipids secreted in blood plasma either upon platelet activation (11) or from brain tumor-derived glioma cells (12). In fact, we have demonstrated that BMSC chemotaxis was very strong in response to S1P (13) and required reorganization of the actin cytoskeleton and remodeling of the extracellular matrix (ECM) through a complex, cooperative signal transduction network involving cell surface matrix metalloproteinase (MMP) activity (14). Currently, the molecular characterization and the nature of that MMP, regulating both BMSC chemotaxis and interaction with the ECM protein microenvironment, remain poorly understood. Recently, we highlighted functional cross-talk between the membrane type-1 MMP (MT1-MMP) and the S1P receptor EDG-1-mediated signaling in BMSC chemotaxis (13). Interestingly, aside from its classical role in ECM proteolysis, MT1-MMP is also involved in transducing crucial intracellular signaling that may control several processes related to BMSC mobilization and cell survival (13)(14)(15)(16).Given that impaired chemotaxis was recently observed in bone marrow cells isolated from a microsomal glucose 6-phos-* This work was supported by a grant of the Natural Sciences and EngineeringResearch Council of Canada (NSERC) (to B. A.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 2 The abbreviations used are: BMSC, bone marrow-derived stromal cell(s); ConA, concanavalin A; ECM, extracellular matrix; G6P, glucose 6-phosphate; G6Pase, glucose-6-phosphatase; G6PT, G6P transporter; MMP, matrix metalloproteinase; MT1-MMP, membrane type-1 MMP; PI, propidium iodine; siRNA, small interfering RNA; S1P, sphingosine 1-phosphate; PBS, phosphate-buffered saline; Wt, wild type; GFP, green fluorescent protein.

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Section: Discussionmentioning

confidence: 99%

MT1-MMP Down-regulates the Glucose 6-Phosphate Transporter Expression in Marrow Stromal Cells

Currie¹,

Fortier²,

Sina³

et al. 2007

Journal of Biological Chemistry

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“…Similarly, Schichor et al demonstrated that VEGF-A contributed to glioma-induced migration of human marrow stromal cells (hMSC) [70] . The authors showed that VEGF-A, but not MCP-1, induced a concentration-dependent increase of hMSC migration.…”

Section: Angiogenic Cytokinesmentioning

confidence: 92%

Stem cells tropism for malignant gliomas

Zhu

2007

Neurosci. Bull.

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Abstract:Various studies have demonstrated the tremendous tropism of stem cells for malignant gliomas, making these cells a potential vehicle for delivery of therapeutic genes to disseminated glioma cells. However, little is known about the mechanisms underlying the glioma-induced tropism of stem cells. Soluble factors including chemokines or growth factors released and expressed by glioma cells at least mediate the tropism of stem cells for gliomas. Here we review the possible mechanisms of stem cells tropism for malignant gliomas.

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“…Glioma and the surrounding inflamed tissue express migratory factors, MCP-1, IL-8, uPA, EGF, and VEGF (20,(31)(32)(33)(34). Among the various factors, we focused on SDF-1· and its receptor CXCR4, which is known to mediate bone marrow-derived cell trafficking under normal and pathologic conditions (35).…”

Section: Discussionmentioning

confidence: 99%

CXCR4-transfected human umbilical cord blood-derived mesenchymal stem cells exhibit enhanced migratory capacity toward gliomas

Park

Ryu²,

Kim³

et al. 2010

Int J Oncol

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Abstract. Mesenchymal stem cells (MSCs) can be used as a delivery vehicle for gene therapy against brain tumors, because these cells have a migratory capacity toward glioma cells. Soluble factors including chemokines or growth factors expressed and released by glioma cells mediate the tropism of MSCs for gliomas. Among them, stromal cell-derived factor-1· (SDF-1·) has been identified as a key molecule related to the tropism of MSC in many cancers containing gliomas. In this study, we found that overexpression of the SDF-1· receptor, CXCR4, on human umbilical cord bloodderived MSCs (hUCB-MSCs) enhanced the migratory capacity of MSCs toward gliomas. We showed that hUCB-MSCs have the migration ability toward the glioma cell lines and primary glioma cells. SDF-1· treatment increased the migration capacity of hUCB-MSCs in a dose-dependent manner and inhibition of SDF-1· or CXCR4 by treatment with the anti-SDF-1· or the CXCR4 antagonist AMD3100 blocked the migration capacity of hUCB-MSCs toward glioma cells. Furthermore, CXCR4-overexpressed hUCB-MSCs (hMSCs-CXCR4) showed a stronger migration capacity toward glioma cells in vitro compared with control MSCs, and also exhibited enhanced migration to glioma cells in an intracranial human malignant glioma xenograft model. These results indicate that SDF-1·/CXCR4 could be involved in recruitment of hUCB-MSCs to glioma cells and that overexpression of CXCR4 may be a useful tool for stem cell-based glioma therapy.

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Vascular endothelial growth factor A contributes to glioma-induced migration of human marrow stromal cells (hMSC)

Cited by 125 publications

References 26 publications

MT1-MMP Down-regulates the Glucose 6-Phosphate Transporter Expression in Marrow Stromal Cells

MT1-MMP Down-regulates the Glucose 6-Phosphate Transporter Expression in Marrow Stromal Cells

Stem cells tropism for malignant gliomas

CXCR4-transfected human umbilical cord blood-derived mesenchymal stem cells exhibit enhanced migratory capacity toward gliomas

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