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.