Author/Authors :
Karnezis، نويسنده , , Tara and Shayan، نويسنده , , Ramin and Caesar، نويسنده , , Carol and Roufail، نويسنده , , Sally and Harris، نويسنده , , Nicole C. and Ardipradja، نويسنده , , Kathryn and Zhang، نويسنده , , You Fang and Williams، نويسنده , , Steven P. and Farnsworth، نويسنده , , Rae H. and Chai، نويسنده , , Ming G. and Rupasinghe، نويسنده , , Thusitha W.T. and Tull، نويسنده , , Dedreia L. and Baldwin، نويسنده , , Megan E. and Sloan، نويسنده , , Erica K. and Fox، نويسنده , , Stephen B. and Achen، نويسنده , , Marc G. and Stacker، نويسنده , , Steven A.، نويسنده ,
Abstract :
Summary
tic metastasis is facilitated by lymphangiogenic growth factors VEGF-C and VEGF-D that are secreted by some primary tumors. We identified regulation of PGDH, the key enzyme in prostaglandin catabolism, in endothelial cells of collecting lymphatics, as a key molecular change during VEGF-D-driven tumor spread. The VEGF-D-dependent regulation of the prostaglandin pathway was supported by the finding that collecting lymphatic vessel dilation and subsequent metastasis were affected by nonsteroidal anti-inflammatory drugs (NSAIDs), known inhibitors of prostaglandin synthesis. Our data suggest a control point for cancer metastasis within the collecting lymphatic endothelium, which links VEGF-D/VEGFR-2/VEGFR-3 and the prostaglandin pathways. Collecting lymphatics therefore play an active and important role in metastasis and may provide a therapeutic target to restrict tumor spread.
