Journal article
VEGF-D Promotes Tumor Metastasis by Regulating Prostaglandins Produced by the Collecting Lymphatic Endothelium
T Karnezis, R Shayan, C Caesar, S Roufail, NC Harris, K Ardipradja, YF Zhang, SP Williams, RH Farnsworth, MG Chai, TWT Rupasinghe, DL Tull, ME Baldwin, EK Sloan, SB Fox, MG Achen, SA Stacker
Cancer Cell | Published : 2012
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-..
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Awarded by Royal Australasian College of Surgeons
Funding Acknowledgements
The authors thank Dr. Maria Macheda for critically reviewing the manuscript, Ms. Janna Taylor for assistance in generating figures, Dr. Bronislaw Pytowski for providing neutralizing VEGFR-2 and VEGFR-3 antibodies, and Dr. Matthias Francois for helpful discussion. This work was funded partly by a Program Grant from the National Health and Medical Research Council of Australia (NHMRC) and by funds from the Operational Infrastructure Support Program provided by the Victorian Government, Australia. S.A.S. and M.G.A. are supported by Senior Research Fellowships from the NHMRC. S.A.S. would like to acknowledge the support of the Pfizer Australia Fellowship. R.S. is supported by the Raelene Boyle Sporting Chance Foundation and Royal Australasian College of Surgeons (RAGS) Foundation Scholarship, and the RAGS Surgeon Scientist Program. S.P.W. is supported by a National Breast Cancer Foundation Doctoral Research Scholarship. N.C.H. and R.H.F. are supported by a Melbourne Research Scholarship from the University of Melbourne, Australia. E.K.S. is supported by a National Breast Cancer Foundation early career award and an NHMRC grant (1008865).