VEGF-D Promotes Tumor Metastasis by Regulating Prostaglandins Produced by the Collecting Lymphatic Endothelium
2012; Cell Press; Volume: 21; Issue: 2 Linguagem: Inglês
10.1016/j.ccr.2011.12.026
ISSN1878-3686
AutoresTara Karnezis, Ramin Shayan, Carol Caesar, Sally Roufail, Nicole C. Harris, Kathryn Ardipradja, You Fang Zhang, Steven P. Williams, Rae H. Farnsworth, Ming G. Chai, Thusitha Rupasinghe, Dedreia Tull, Megan E. Baldwin, Erica K. Sloan, Stephen B. Fox, Marc G. Achen, Steven A. Stacker,
Tópico(s)Sympathectomy and Hyperhidrosis Treatments
ResumoLymphatic 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.
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