title: Granulocyte-colony stimulating factor promotes lung metastasis through mobilization of Ly6G+Ly6C+ granulocytes.
abstract: Priming of the organ-specific premetastatic sites is thought to be an important yet incompletely understood step during metastasis. In this study, we show that the metastatic tumors we examined overexpress granulocyte-colony stimulating factor (G-CSF), which expands and mobilizes Ly6G+Ly6C+ granulocytes and facilitates their subsequent homing at distant organs even before the arrival of tumor cells. Moreover, G-CSF-mobilized Ly6G+Ly6C+ cells produce the Bv8 protein, which has been implicated in angiogenesis and mobilization of myeloid cells. Anti-G-CSF or anti-Bv8 antibodies significantly reduced lung metastasis. Transplantation of Bv8 null fetal liver cells into lethally irradiated hosts also reduced metastasis. We identified an unexpected role for Bv8: the ability to stimulate tumor cell migration through activation of one of the Bv8 receptors, prokineticin receptor (PKR)-1. Finally, we show that administration of recombinant G-CSF is sufficient to increase the numbers of Ly6G+Ly6C+ cells in organ-specific metastatic sites and results in enhanced metastatic ability of several tumors.
authors.affiliation: Genentech Inc, South San Francisco, CA 94080, USA.
authors.forename: Marcin
authors.initials: M
authors.lastname: Kowanetz
authors.forename: Xiumin
authors.initials: X
authors.lastname: Wu
authors.forename: John
authors.initials: J
authors.lastname: Lee
authors.forename: Martha
authors.initials: M
authors.lastname: Tan
authors.forename: Thijs
authors.initials: T
authors.lastname: Hagenbeek
authors.forename: Xueping
authors.initials: X
authors.lastname: Qu
authors.forename: Lanlan
authors.initials: L
authors.lastname: Yu
authors.forename: Jed
authors.initials: J
authors.lastname: Ross
authors.forename: Nina
authors.initials: N
authors.lastname: Korsisaari
authors.forename: Tim
authors.initials: T
authors.lastname: Cao
authors.forename: Hani
authors.initials: H
authors.lastname: Bou-Reslan
authors.forename: Dara
authors.initials: D
authors.lastname: Kallop
authors.forename: Robby
authors.initials: R
authors.lastname: Weimer
authors.forename: Mary J C
authors.initials: MJ
authors.lastname: Ludlam
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Kaminker
authors.forename: Zora
authors.initials: Z
authors.lastname: Modrusan
authors.forename: Nicholas
authors.initials: N
authors.lastname: van Bruggen
authors.forename: Franklin V
authors.initials: FV
authors.lastname: Peale
authors.forename: Richard
authors.initials: R
authors.lastname: Carano
authors.forename: Y Gloria
authors.initials: YG
authors.lastname: Meng
authors.forename: Napoleone
authors.initials: N
authors.lastname: Ferrara
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000276:immunology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D020869:Gene Expression Profiling; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000494:pharmacology*; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D016513:Mice, SCID; D046228:Microarray Analysis; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology
chemical_list: D000950:Antigens, Ly; D000970:Antineoplastic Agents; C494192:Ly-6C antigen, mouse; C480309:Ly6G antigen, mouse; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor