Reference: Tara 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 W.T. Rupasinghe, Dedreia L. Tull, Megan E. Baldwin, Erica K. Sloan, Stephen B. Fox, Marc G. Achen, Steven A. Stacker, 'VEGF-D Promotes Tumor Metastasis by Regulating Prostaglandins Produced by the Collecting Lymphatic Endothelium', Cancer Cell, 21, 2, 14 February 2012, pp. 181–195
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Prostaglandin production is increased by VEGF-D+ which is produced by metastatic cancer cells. Increased prostaglandin leads to dilation of lymphatic vessels allowing cancer cells to spread. Aspirin prevents cancer by inhibiting prostaglandin production, narrowing lymphatic vessels, restricting spread of cancer.
Abstract: Lymphatic 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.
Prostaglandin production is increased by VEGF-D+ which is produced by metastatic cancer cells. Increased prostaglandin leads to dilation of lymphatic vessels allowing cancer cells to spread. Aspirin prevents cancer by inhibiting prostaglandin production, narrowing lymphatic vessels, restricting spread of cancer.
Abstract: Lymphatic 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.
