Blocking Neuropilin-2 Function Inhibits Tumor Cell Metastasis

Metastasis, which commonly uses lymphatics, accounts for much of the mortality associated with cancer. The vascular endothelial growth factor (VEGF)-C coreceptor, neuropilin-2 (Nrp2), modulates but is not necessary for developmental lymphangiogenesis, and its significance for metastasis is unknown....

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Bibliographic Details
Published in:Cancer cell 2008-04, Vol.13 (4), p.331-342
Main Authors: Caunt, Maresa, Mak, Judy, Liang, Wei-Ching, Stawicki, Scott, Pan, Qi, Tong, Raymond K., Kowalski, Joe, Ho, Calvin, Reslan, Hani Bou, Ross, Jed, Berry, Leanne, Kasman, Ian, Zlot, Constance, Cheng, Zhiyong, Le Couter, Jennifer, Filvaroff, Ellen H., Plowman, Greg, Peale, Franklin, French, Dorothy, Carano, Richard, Koch, Alexander W., Wu, Yan, Watts, Ryan J., Tessier-Lavigne, Marc, Bagri, Anil
Format: Article
Language:English
Subjects:
Animals
Antibodies, Blocking - pharmacology
Antibody Specificity - drug effects
Bacteriophages
Cell Line
CELLCYCLE
Disease Models, Animal
Enzyme Activation - drug effects
Humans
Lung Neoplasms - secondary
Lymph Nodes - pathology
Lymphangiogenesis - drug effects
Lymphatic Metastasis - prevention & control
Lymphatic System - drug effects
Lymphatic System - pathology
Mice
Neoplasm Metastasis - prevention & control
Neoplasms - pathology
Neuropilin-2 - antagonists & inhibitors
Neuropilin-2 - metabolism
Receptors, Vascular Endothelial Growth Factor - metabolism
Vascular Endothelial Growth Factor C - metabolism
Vascular Endothelial Growth Factor Receptor-2 - metabolism
Xenograft Model Antitumor Assays
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Summary:Metastasis, which commonly uses lymphatics, accounts for much of the mortality associated with cancer. The vascular endothelial growth factor (VEGF)-C coreceptor, neuropilin-2 (Nrp2), modulates but is not necessary for developmental lymphangiogenesis, and its significance for metastasis is unknown. An antibody to Nrp2 that blocks VEGFC binding disrupts VEGFC-induced lymphatic endothelial cell migration, but not proliferation, in part independently of VEGF receptor activation. It does not affect established lymphatics in normal adult mice but reduces tumoral lymphangiogenesis and, importantly, functional lymphatics associated with tumors. It also reduces metastasis to sentinel lymph nodes and distant organs, apparently by delaying the departure of tumor cells from the primary tumor. Our results demonstrate that Nrp2, which was originally identified as an axon-guidance receptor, is an attractive target for modulating metastasis.
ISSN:1535-6108
1878-3686
DOI:10.1016/j.ccr.2008.01.029