VEGF-D promotes tumor metastasis by regulating prostaglandins produced by the collecting lymphatic endothelium.

TitleVEGF-D promotes tumor metastasis by regulating prostaglandins produced by the collecting lymphatic endothelium.
Publication TypeJournal Article
Year of Publication2012
AuthorsKarnezis T, Shayan R, Caesar C, Roufail S, Harris NC, Ardipradja K, Zhang YFang, Williams SP, Farnsworth RH, Chai MG, Rupasinghe TWT, Tull DL, Baldwin ME, Sloan EK, Fox SB, Achen MG, Stacker SA
JournalCancer Cell
Volume21
Issue2
Pagination181-95
Date Published2012 Feb 14
ISSN1878-3686
KeywordsAnimals, Anti-Inflammatory Agents, Cell Transformation, Neoplastic, Endothelium, Lymphatic, Female, Gene Expression Regulation, Neoplastic, Humans, Lymphangiogenesis, Lymphatic Metastasis, Lymphatic System, Lymphatic Vessels, Mice, Mice, Inbred NOD, Mice, SCID, Prostaglandins, Vascular Endothelial Growth Factor D, Vascular Endothelial Growth Factor Receptor-2, Vascular Endothelial Growth Factor Receptor-3
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.

DOI10.1016/j.ccr.2011.12.026
Alternate JournalCancer Cell
PubMed ID22340592