Linked Life Data

11877295

Source:http://linkedlifedata.com/resource/pubmed/id/11877295

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2002-3-5
pubmed:abstractText
Similar to solid tumors, growth of leukemias may also be angiogenesis dependent. Furthermore, tyrosine kinase receptors specific to endothelial cells are expressed on certain subsets of leukemias. We have previously demonstrated the existence of a VEGF/VEGFR-2 autocrine loop on leukemic cells that supports their growth and migration. Here, we demonstrate that in response to leukemia-derived proangiogenic and proinflammatory cytokines such as basic fibroblast growth factor and IL-1, endothelial cells release increasing amounts of another vascular endothelial growth factor (VEGF) family member, VEGF-C. In turn, interaction of VEGF-C with its receptor VEGFR-3 (FLT-4) promotes leukemia survival and proliferation. We demonstrate in 2 cell lines and 5 FLT-4(+) leukemias that VEGF-C and a mutant form of the molecule that lacks the KDR-binding motif induce receptor phosphorylation, leukemia proliferation, and increased survival, as determined by increased Bcl-2/Bax ratios. Moreover, VEGF-C protected leukemic cells from the apoptotic effects of 3 chemotherapeutic agents. Because most leukemic cells release proangiogenic as well as proinflammatory cytokines, our data suggest that the generation of a novel paracrine angiogenic loop involving VEGF-C and FLT-4 may promote the survival of a subset of leukemias and protect them from chemotherapy-induced apoptosis. These results identify the VEGF-C/FLT-4 pathway as a novel therapeutic target for the treatment of subsets of acute leukemia.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
99
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2179-84
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11877295-Cell Division, pubmed-meshheading:11877295-Cell Survival, pubmed-meshheading:11877295-Cytokines, pubmed-meshheading:11877295-Drug Resistance, Neoplasm, pubmed-meshheading:11877295-Endothelial Growth Factors, pubmed-meshheading:11877295-Endothelium, Vascular, pubmed-meshheading:11877295-Humans, pubmed-meshheading:11877295-Leukemia, pubmed-meshheading:11877295-Paracrine Communication, pubmed-meshheading:11877295-Receptor Protein-Tyrosine Kinases, pubmed-meshheading:11877295-Receptors, Growth Factor, pubmed-meshheading:11877295-Signal Transduction, pubmed-meshheading:11877295-Tumor Cells, Cultured, pubmed-meshheading:11877295-Umbilical Cord, pubmed-meshheading:11877295-Vascular Endothelial Growth Factor C, pubmed-meshheading:11877295-Vascular Endothelial Growth Factor Receptor-3
pubmed:year
2002
pubmed:articleTitle
Vascular endothelial growth factor (VEGF)-C signaling through FLT-4 (VEGFR-3) mediates leukemic cell proliferation, survival, and resistance to chemotherapy.
pubmed:affiliation
Division of Hematology/Oncology, Weill Medical College of Cornell University, 1300 York Ave, New York, NY 10021, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't