title: Blocking neuropilin-2 function inhibits tumor cell metastasis.
abstract: 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.
authors.affiliation: Tumor Biology and Angiogenesis, Genentech, Inc., South San Francisco, CA 94080, USA.
authors.forename: Maresa
authors.initials: M
authors.lastname: Caunt
authors.forename: Judy
authors.initials: J
authors.lastname: Mak
authors.forename: Wei-Ching
authors.initials: WC
authors.lastname: Liang
authors.forename: Scott
authors.initials: S
authors.lastname: Stawicki
authors.forename: Qi
authors.initials: Q
authors.lastname: Pan
authors.forename: Raymond K
authors.initials: RK
authors.lastname: Tong
authors.forename: Joe
authors.initials: J
authors.lastname: Kowalski
authors.forename: Calvin
authors.initials: C
authors.lastname: Ho
authors.forename: Hani Bou
authors.initials: HB
authors.lastname: Reslan
authors.forename: Jed
authors.initials: J
authors.lastname: Ross
authors.forename: Leanne
authors.initials: L
authors.lastname: Berry
authors.forename: Ian
authors.initials: I
authors.lastname: Kasman
authors.forename: Constance
authors.initials: C
authors.lastname: Zlot
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Cheng
authors.forename: Jennifer
authors.initials: J
authors.lastname: Le Couter
authors.forename: Ellen H
authors.initials: EH
authors.lastname: Filvaroff
authors.forename: Greg
authors.initials: G
authors.lastname: Plowman
authors.forename: Franklin
authors.initials: F
authors.lastname: Peale
authors.forename: Dorothy
authors.initials: D
authors.lastname: French
authors.forename: Richard
authors.initials: R
authors.lastname: Carano
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Koch
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Watts
authors.forename: Marc
authors.initials: M
authors.lastname: Tessier-Lavigne
authors.forename: Anil
authors.initials: A
authors.lastname: Bagri
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000918:Antibody Specificity / Q000187:drug effects; D001435:Bacteriophages; D002460:Cell Line; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D008198:Lymph Nodes / Q000473:pathology; D042583:Lymphangiogenesis / Q000187:drug effects; D008207:Lymphatic Metastasis / Q000517:prevention & control; D008208:Lymphatic System / Q000187:drug effects / Q000473:pathology; D051379:Mice; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009369:Neoplasms / Q000473:pathology*; D039943:Neuropilin-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D019138:Antibodies, Blocking; D039943:Neuropilin-2; D042582:Vascular Endothelial Growth Factor C; D040262:Receptors, Vascular Endothelial Growth Factor; D040301:Vascular Endothelial Growth Factor Receptor-2