Flt-1 Signaling in Macrophages Promotes Glioma Growth <i>In vivo</i>

Kerber, Mark; Reiss, Yvonne; Wickersheim, Anke; Jugold, Manfred; Kießling, Fabian; Heil, Matthias; Tchaikovski, Vadim; Waltenberger, Johannes; Shibuya, Masabumi; Plate, Karl H.; Machein, Márcia Regina

doi:10.1158/0008-5472.can-07-6241

Cited by 145 publications

(131 citation statements)

References 46 publications

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“…Bone stromal cells secrete some growth factors which promote the proliferation of high bone metastasis potential cells. Our hypothesis is supported by the finding that flt-1 signaling in bone marrow derived cells was required for its activity on the growth of glioma (21).…”

Section: Discussionsupporting

confidence: 70%

Discrepancy of biologic behavior influenced by bone marrow derived cells in lung cancer

et al. 2010

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Abstract. Disseminated cancer cells may initially require local nutrients and growth factors to thrive and survive in bone marrow. However, data on the influence of bone marrow derived cells (BMDC, also called bone stromal cells in some publications) on lung cancer cells is largely unexplored. This study explored the mechanism of how bone stromal factors contribute to the bone tropism in lung cancer. The difference among lung cancer cell lines in their abilities to metastasize to bone was found using the SCID animal model. Supernatant of bone marrow aspiration (BM) and condition medium from human bone stromal cells (BSC) were used to study the activity of bone stromal factors. We found bone stromal factors significantly increased the proliferation, invasion, adhesion and expression of angiogenosis-related factors, and inhibited the apoptosis for high bone metastasis H460 lung cancer cells. These biologic effects were not seen in SPC-A1 or A549 cells, which are low bone metastasis lung cancer cells. Adhesion of H460 cells to surface coated with bone stromal cells can activate some signal transduction pathways, and alter the expression of adhesion associated factors, including integrin ß 3 and ADAMTS-1, two potential targets related with bone metastasis. We concluded that bone marrow derived cells had a profound effect on biological behavior of lung cancers, therefore favoring the growth of lung cancer cells in bone.

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Section: Discussionsupporting

confidence: 70%

Discrepancy of biologic behavior influenced by bone marrow derived cells in lung cancer

et al. 2010

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“…Moreover, although blockade of VEGFR1 activity decreases the number of TAMs in certain tumors, it does not completely suppress myeloid BMDC infiltration in growing primary tumors or lung metastases (9,25,26). This may be due, at least in part, to the inability of VEGF/VEGFR1 inhibition to prevent Gr-1 + myeloid cell infiltration into tumors (9,10).…”

Section: Discussionmentioning

confidence: 99%

C-X-C receptor type 4 promotes metastasis by activating p38 mitogen-activated protein kinase in myeloid differentiation antigen (Gr-1)-positive cells

Hiratsuka

Duda

Huang

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Increasing evidence suggests that myeloid bone marrow-derived cells (BMDCs) play a critical role in lung metastasis. Blockade of VEGF receptor 1 (VEGFR1) has been proposed as a potential strategy to limit myeloid BMDC recruitment to tumors. However, preclinical evidence indicates that this strategy may not be effective in all tumors. Thus, establishing which molecular mechanisms are responsible for the "escape" of these BMDCs from VEGFR1 inhibition would facilitate development of strategies to control metastasis. Here, we report the complementary role of the chemokine (C-X-C motif) ligand 12/C-X-C chemokine receptor 4 (CXCR4) and VEGF/VEGFR1 pathways in promoting lung metastasis in mice via BMDC recruitment using chimeric mice with deficiency in CXCR4 and VEGFR1-tyrosine kinase in the BMDCs. We first demonstrate that CXCR4 activity is essential for recruitment of myeloid differentiation antigen (Gr-1)-positive BMDCs, whereas VEGFR1 activity is responsible for macrophage recruitment in established tumors. Inhibition of both VEGFR1 and CXCR4 signaling in myeloid BMDCs exerted greater effects on tumor vascular density, growth, and lung metastasis than inhibition of VEGFR1 alone. These effects were reproduced after pharmacologic inhibition of CXCR4 with AMD3100. VEGFR1 and CXCR4 independently exerted a promigratory effect in myeloid BMDCs by activating p38 mitogen-activating protein kinase. Thus, combining CXCR4 blockade with inhibition of VEGFR1 may induce greater tumor growth delay and prevent or inhibit metastasis.

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“…A dynamic relationship forms between the pre-neoplastic/ neoplastic and non-neoplastic stromal cell populations through stromagen and gliomagens release, which together facilitate tumorigenesis, tumor maintenance and glioma progression. endothelial growth factor (Forstreuter et al, 2002;Kerber et al, 2008), hepatocyte growth factor (Badie et al, 1999;Kunkel et al, 2001), monocyte chemoattractant protein-1 (Martinet et al, 1992;Leung et al, 1997) and the chemokine CX3CL1 (fractalkine) through activation of the CX3CR1 receptor (Held-Feindt et al, 2010). Monocyte chemoattractant protein-1 can also increase the surface expression of CX3CR1 on microglia (Green et al, 2006), thus providing amplification circuits for further microglia recruitment.…”

Section: Stromal Determinants Of Glioma Formation and Growthmentioning

confidence: 99%

The ecology of brain tumors: lessons learned from neurofibromatosis-1

Pong

Gutmann

2010

Oncogene

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Traditionally, cancer studies have primarily focused on mutations that activate growth or survival pathways in susceptible pre-neoplastic/neoplastic cells. However, recent research has revealed a critical role for nonneoplastic cells within the tumor microenvironment in the process of cancer formation and progression. In addition, the existence of regional and developmental variations in susceptible cell types and supportive microenvironments support a model of tumorigenesis in which the dynamic symbiotic relationship between neoplastic and non-neoplastic cell types dictate where and when cancers form and grow. In this review, we highlight advances in neurofibromatosis type 1 (NF1) genetically engineered mouse brain tumor (glioma) modeling to reveal how cellular and molecular heterogeneity in both the pre-neoplastic/ neoplastic and non-neoplastic cellular compartments contribute to gliomagenesis and glioma growth.

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Flt-1 Signaling in Macrophages Promotes Glioma Growth In vivo

Abstract: Several lines of evidence indicate that Flt-1, a fms-like tyrosine kinase receptor, which

Cited by 145 publications

References 46 publications

Discrepancy of biologic behavior influenced by bone marrow derived cells in lung cancer

Discrepancy of biologic behavior influenced by bone marrow derived cells in lung cancer

C-X-C receptor type 4 promotes metastasis by activating p38 mitogen-activated protein kinase in myeloid differentiation antigen (Gr-1)-positive cells

The ecology of brain tumors: lessons learned from neurofibromatosis-1

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