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

Tara Karnezis; Ramin Shayan; Carol Caesar; Sally Roufail; Nicole C Harris; Kathryn Ardipradja; You F Zhang; Steven P Williams; Rae H Farnsworth; Ming Gene Chai; Thusitha Wasantha Thilaka Rupasinghe; Dedreia Tull; Megan E Baldwin; Erica Kate Sloan; Stephen B Fox; Marc G Achen; Steven A Stacker

doi:10.1016/j.ccr.2011.12.026

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

Tara Karnezis, Ramin Shayan, Carol Caesar, Sally Roufail, Nicole C Harris, Kathryn Ardipradja, You F Zhang, Steven P Williams, Rae H Farnsworth, Ming Gene Chai, Thusitha Wasantha Thilaka Rupasinghe, Dedreia Tull, Megan E Baldwin, Erica Kate Sloan, Stephen B Fox, Marc G Achen, Steven A Stacker

Research output: Contribution to journal › Article › Research › peer-review

237 Citations (Scopus)

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-DNEGFR-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.

Original language	English
Pages (from-to)	181 - 195
Number of pages	15
Journal	Cancer Cell
Volume	21
Issue number	2
DOIs	https://doi.org/10.1016/j.ccr.2011.12.026
Publication status	Published - 2012

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Karnezis, T., Shayan, R., Caesar, C., Roufail, S., Harris, N. C., Ardipradja, K., Zhang, Y. F., Williams, S. P., Farnsworth, R. H., Chai, M. G., Rupasinghe, T. W. T., Tull, D., Baldwin, M. E., Sloan, E. K., Fox, S. B., Achen, M. G., & Stacker, S. A. (2012). VEGF-D promotes tumor metastasis by regulating prostaglandins produced by the collecting lymphatic endothelium. Cancer Cell, 21(2), 181 - 195. https://doi.org/10.1016/j.ccr.2011.12.026

@article{8a3434f5ae0e4403832cfc70101b0045,

title = "VEGF-D promotes tumor metastasis by regulating prostaglandins produced by the collecting lymphatic endothelium",

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-DNEGFR-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.",

author = "Tara Karnezis and Ramin Shayan and Carol Caesar and Sally Roufail and Harris, {Nicole C} and Kathryn Ardipradja and Zhang, {You F} and Williams, {Steven P} and Farnsworth, {Rae H} and Chai, {Ming Gene} and Rupasinghe, {Thusitha Wasantha Thilaka} and Dedreia Tull and Baldwin, {Megan E} and Sloan, {Erica Kate} and Fox, {Stephen B} and Achen, {Marc G} and Stacker, {Steven A}",

year = "2012",

doi = "10.1016/j.ccr.2011.12.026",

language = "English",

volume = "21",

pages = "181 -- 195",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

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Karnezis, T, Shayan, R, Caesar, C, Roufail, S, Harris, NC, Ardipradja, K, Zhang, YF, Williams, SP, Farnsworth, RH, Chai, MG, Rupasinghe, TWT, Tull, D, Baldwin, ME, Sloan, EK, Fox, SB, Achen, MG & Stacker, SA 2012, 'VEGF-D promotes tumor metastasis by regulating prostaglandins produced by the collecting lymphatic endothelium', Cancer Cell, vol. 21, no. 2, pp. 181 - 195. https://doi.org/10.1016/j.ccr.2011.12.026

TY - JOUR

T1 - VEGF-D promotes tumor metastasis by regulating prostaglandins produced by the collecting lymphatic endothelium

AU - Karnezis, Tara

AU - Shayan, Ramin

AU - Caesar, Carol

AU - Roufail, Sally

AU - Harris, Nicole C

AU - Ardipradja, Kathryn

AU - Zhang, You F

AU - Williams, Steven P

AU - Farnsworth, Rae H

AU - Chai, Ming Gene

AU - Rupasinghe, Thusitha Wasantha Thilaka

AU - Tull, Dedreia

AU - Baldwin, Megan E

AU - Sloan, Erica Kate

AU - Fox, Stephen B

AU - Achen, Marc G

AU - Stacker, Steven A

PY - 2012

Y1 - 2012

N2 - 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-DNEGFR-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.

AB - 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-DNEGFR-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.

UR - http://www.cell.com/cancer-cell/home

U2 - 10.1016/j.ccr.2011.12.026

DO - 10.1016/j.ccr.2011.12.026

M3 - Article

SN - 1535-6108

VL - 21

SP - 181

EP - 195

JO - Cancer Cell

JF - Cancer Cell

IS - 2

ER -

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

Abstract

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