Modulation of human NK cell lines by vascular endothelial growth factor and receptor VEGFR-1 (FLT-1).
Our laboratory has previously reported that natural killer (NK) cells bind to angiogenic microvessels in established cancer metastases. Vascular endothelial growth factor (VEGF) plays an important role in solid tumor angiogenesis by enhancing new blood vessel formation to transport nutrients and oxygen into tumors. Here we report that the human natural killer cell lines, NK-92 and YT, express the mRNA message and protein product for VEGF-B and its receptor, VEGFR-1/Flt-1. While stimulation of these cells by the potent angiogenic factor VEGF-A165, which also binds to VEGFR-1, does not alter the proliferation of the cells, it does increase adhesion to a model basement membrane-like extracellular matrix, Matrigel. VEGF-A165 also induces NK cell binding to human microvascular endothelial cells in newly forming but not established microvessels in vitro. These results suggest that human NK cells produce an angiogenic factor which may be involved in autocrine and paracrine regulations of angiogenesis. VEGF-A165 appears to stimulate NK cell adhesion to the microvasculature within established cancer metastases.
Chen
Wilson S
WS
Department of Molecular Biology and Immunology, Institute for Cancer Research, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX 76107-2118, USA. rgoldfar@hsc.unt.edu
Kitson
Richard P
RP
Goldfarb
Ronald H
RH
D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D003094:Collagen / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007797:Laminin / Q000378:metabolism; D008222:Lymphokines / Q000494:pharmacology*; D020033:Protein Isoforms / Q000494:pharmacology; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A; D042561:Vascular Endothelial Growth Factor B; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism*; D042442:Vascular Endothelial Growth Factors
D017931:DNA Primers; D004338:Drug Combinations; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D007797:Laminin; D008222:Lymphokines; D020033:Protein Isoforms; D011509:Proteoglycans; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042561:Vascular Endothelial Growth Factor B; D042442:Vascular Endothelial Growth Factors; C059485:matrigel; D003094:Collagen; D040281:Vascular Endothelial Growth Factor Receptor-1