Vascular progenitors derived from murine bone marrow stromal cells are regulated by fibroblast growth factor and are avidly recruited by vascularizing tumors

Annabi, Borhane; Naud, Emmanuelle; Lee, Ying‐Ta; Eliopoulos, Nicoletta; Galipeau, Jacques

doi:10.1002/jcb.10763

Cited by 95 publications

(83 citation statements)

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“…However, MSCs proliferation was not observed when MSCs were injected alone without malignant cells [13] . Similar results were obtained by Annabi et al [16] after subcutaneous MSC co-injection with malignant glioma cells and by Karnoub et al [17] with human breast cancer cells. Intramuscular injection of hAMSCs in mice showed that the implanted cells tended to maintain a steady state population, did not proliferate rapidly after implantation, and resulted in neither detectable chromosomal abnormalities nor tumors after 8 mo [12] .…”

Section: Introductionsupporting

confidence: 87%

Fate of human AMSCs over the short and long term after subcutaneous injection in immunodeficient mice

Lopez-Iglesias¹

2011

WJSC

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AIM:To study the ability of human adipose-derived mesenchymal stem cells (AMSCs) to survive over the short and long term, their biodistribution and their biosafety in vivo in tumor-prone environments. METHODS:We subcutaneously injected human AMSCs from different human donors into immunodeficient SCID mice over both short-(2 and 4 mo) and long-(17 mo) term in young, and aged tumor-prone mice. Presence of human cells was studied by immunohistochemistry and polymerase chain reaction analysis in all organs of injected mice. RESULTS:Subcutaneously injected AMSCs did not form teratomas at any time point. They did not migrate but remained at the site of injection regardless of animal age, and did not fuse with host cells in any organ examined. AMSCs survived in vivo for at least 17 mo after injection, and differentiated into fibroblasts of the subdermic connective tissue and into mature adipocytes of fat tissue, exclusively at the site of injection. CONCLUSION:Our results support the assertion that AMSC may be safe candidates for therapy when injected subcutaneously because of their long term inability to form teratomas.

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Section: Introductionsupporting

confidence: 87%

Fate of human AMSCs over the short and long term after subcutaneous injection in immunodeficient mice

Lopez-Iglesias¹

2011

WJSC

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“…The latter events have, interestingly, also been shown to involve MT1-MMP functions such as in cell migration (46) and in ERK and in RhoA/ROK signaling (14,15,47). More recently, we have revealed several of these MT1-MMP roles in regulating the angiogenic and chemotactic properties of BMSC in response to hypoxia (36) and to brain tumor-derived U-87 glioma cells in vitro and in vivo (48). Interestingly, hypoxia increased MT1-MMP and Egr-1 levels in BMSC (36), a condition that lead to cell death (49).…”

Section: Discussionmentioning

confidence: 97%

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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“…The interaction between MSCs and tumor cells are not limited to homing, but also promote tumor progression. Several reports suggested MSCs could contribute to the growth and progression of some malignant tumors such as melanoma, adenocarcinoma, and breast cancer (16)(17)(18) through the modulation of immune system (9,16) and tumor microenvironment with angiogenic induction (19,20) (21). Various adhesion molecules and chemokines including integrins and CXCL12-CXCR4 axis are involved in MSCs migration and tumor progression; however, the detailed mechanism by which MSCs interact with tumor cells remains unknown.…”

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Mesenchymal stem cells promote tumor engraftment and metastatic colonization in rat osteosarcoma model

Tsukamoto

Honoki

Fujii³

et al. 2011

Int J Oncol

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Abstract.Although mesenchymal stem cells (MSCs) are considered to be the cells of origin for most sarcomas, the role of MSCs as a source of tumor stroma is not fully understood in this tumor type. The current study investigated whether MSCs affect the tumor growth and metastatic ability in rat osteosarcoma model. Results from subcutaneous co-implantation of rat osteosarcoma COS1NR cells, established in our laboratory, with rat MSCs isolated from femur bone marrow showed that the incidence of tumor formation and tumor growth rate was higher until 5 weeks compared to COS1NR cell inoculation alone. However, no difference was observed in tumor growth afterwards and in the number of metastatic nodules at 9 weeks (0.75 vs. 1.2). Intravenous MSC injection at weeks 3 and 5 after subcutaneous inoculation of COS1NR cells significantly increased the number of lung nodules in the group with MSC injection compared to the group without MSC injection (17.33 vs. 2.0), while no difference was observed in subcutaneous tumor growth between those groups. Pathway analysis from gene expression profile identified that genes involved in focal adhesion, cytokine-cytokine receptor and extracellular matrix-receptor pathways such as CAMs (ICAM and VCAM)-integrins were highly expressed in MSCs, possibly participating in the tumor progression of osteosarcoma. These results suggest that MSCs could provide a source of microenvironments for osteosarcoma cells, and might enhance the ability of settlement and colonization which lead to early onset of growth and metastasis, possibly through their activated pathways interaction. IntroductionHistoric landmark of tumor microenvironment research was proposed as the 'seed and soil' hypothesis by Stephen Paget 120 years ago (1), and the importance of the microenvironment and stroma in the evolution and progression of solid tumors has drawn renewed interest in recent years. A complex structure of mixed cell types and tissues with endothelial cells, immune cells, stromal cells and extracellular matrix is essential for the growth and progression of solid tumors (2). Although all of these components in the tumor are integral in carcinogenesis and metastasis, the stroma is considered to be a 'co-conspirator' in the evolution and progression of the disease (3). Among the stromal elements, the progenitor cells of the stroma, the mesenchymal stem cells (MSCs), have been receiving focused attention lately.Mesenchymal stem cells (MSCs) are mainly derived from bone marrow, non-hematopoietic precursor cells possessing differentiation potential to skeletal mesodermal lineages such as osteoblasts, chondrocytes and adipocytes as well as some extra-mesodermal cell types including neural, pancreatic and hepatocytic phenotypes with strong proliferative capacity (4-6), and are of increasing interest as the future therapeutic tool in regenerative medicine (7,8). MSCs also display immune suppressive properties which could be the potentially exploited for therapeutic treatment of auto-immune diseases and the reduction of gra...

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Vascular progenitors derived from murine bone marrow stromal cells are regulated by fibroblast growth factor and are avidly recruited by vascularizing tumors

Cited by 95 publications

References 50 publications

Fate of human AMSCs over the short and long term after subcutaneous injection in immunodeficient mice

Fate of human AMSCs over the short and long term after subcutaneous injection in immunodeficient mice

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

Mesenchymal stem cells promote tumor engraftment and metastatic colonization in rat osteosarcoma model

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