Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2008-9-16
pubmed:abstractText
Several lines of evidence indicate that Flt-1, a fms-like tyrosine kinase receptor, which binds to vascular endothelial growth factor (VEGF)-A, VEGF-B, and PlGF, is a positive regulator of angiogenesis in the context of tumor growth and metastasis. However, the molecular basis of its action is still not clear. Besides endothelial cells, Flt-1 is also expressed by other different cell types, including myeloid hematopoeitic cells (monocytes and macrophages). To examine the functions of Flt-1 expressed by bone marrow-derived myeloid cells in supporting tumor growth and angiogenesis, Flt-1 tyrosine kinase-deficient (Flt-1 TK-/-) bone marrow cells were transplanted into lethally irradiated syngeneic recipients. After hematopoietic reconstitution, we orthotopically implanted syngeneic wild-type glioma cells or glioma cells overexpressing either VEGF(164) or PlGF-2. Loss of Flt-1 signaling in bone marrow-derived myeloid cells led to a significant decrease in tumor volume and vascularization in gliomas. VEGF but not PlGF overexpressed by glioma cells restored the tumor growth rate in Flt-1 TK-/- bone marrow chimera. VEGF and PlGF overexpression by tumor cells induced an accumulation of bone marrow-derived myeloid cells into tumor tissue. This infiltration was decreased in tumors grown in Flt-1 TK-/- bone marrow chimeras. When investigating chemokines and growth factors involved in myeloid cell recruitment, we determined elevated SDF-1/CXCL12 levels in VEGF- and PlGF-overexpressing tumors. Collectively, these results suggest that Flt-1 signaling in myeloid cells is essential to amplify the angiogenic response and to promote glioma growth.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1538-7445
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
68
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7342-51
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18794121-Animals, pubmed-meshheading:18794121-Bone Marrow Cells, pubmed-meshheading:18794121-Capillary Permeability, pubmed-meshheading:18794121-Cell Growth Processes, pubmed-meshheading:18794121-Chemokine CXCL12, pubmed-meshheading:18794121-Chimera, pubmed-meshheading:18794121-Glioma, pubmed-meshheading:18794121-Macrophages, pubmed-meshheading:18794121-Mice, pubmed-meshheading:18794121-Mice, Inbred C57BL, pubmed-meshheading:18794121-Mice, Transgenic, pubmed-meshheading:18794121-Myeloid Cells, pubmed-meshheading:18794121-Neovascularization, Pathologic, pubmed-meshheading:18794121-Proteins, pubmed-meshheading:18794121-Signal Transduction, pubmed-meshheading:18794121-Transfection, pubmed-meshheading:18794121-Vascular Endothelial Growth Factor A, pubmed-meshheading:18794121-Vascular Endothelial Growth Factor Receptor-1
pubmed:year
2008
pubmed:articleTitle
Flt-1 signaling in macrophages promotes glioma growth in vivo.
pubmed:affiliation
Tumor Angiogenesis Research Group, Department of Neurosurgery, University of Freiburg, Freiburg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't