Author/Authors :
Caunt، نويسنده , , Maresa and Mak، نويسنده , , Judy and Liang، نويسنده , , Wei-Ching and Stawicki، نويسنده , , Scott and Pan، نويسنده , , Qi and Tong، نويسنده , , Raymond K. and Kowalski، نويسنده , , Joe and Ho، نويسنده , , Calvin and Reslan، نويسنده , , Hani Bou and Ross، نويسنده , , Jed and Berry، نويسنده , , Leanne and Kasman، نويسنده , , Ian and Zlot، نويسنده , , Constance and Cheng، نويسنده , , Zhiyong and Le Couter، نويسنده , , Jennifer and Filvaroff، نويسنده , , Ellen H. and Plowman، نويسنده , , Greg and Peale، نويسنده , , Franklin and French، نويسنده , , Dorothy and Carano، نويسنده , , Richard and Koch، نويسنده , , Alexander W. and Wu، نويسنده , , Yan and Watts، نويسنده , , Ryan J. and Tessier-Lavigne، نويسنده , , Marc and Bagri، نويسنده , , Anil، نويسنده ,
Abstract :
Summary
asis, 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.
