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.
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Authors | Marcin Kowanetz, Xiumin Wu, John Lee, Martha Tan, Thijs Hagenbeek, Xueping Qu, Lanlan Yu, Jed Ross, Nina Korsisaari, Tim Cao, Hani Bou-Reslan, Dara Kallop, Robby Weimer, Mary J C Ludlam, Joshua S Kaminker, Zora Modrusan, Nicholas van Bruggen, Franklin V Peale, Richard Carano, Y Gloria Meng, Napoleone Ferrara |
Journal | Proceedings of the National Academy of Sciences of the United States of America
(Proc Natl Acad Sci U S A)
Vol. 107
Issue 50
Pg. 21248-55
(Dec 14 2010)
ISSN: 1091-6490 [Electronic] United States |
PMID | 21081700
(Publication Type: Journal Article)
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Chemical References |
- Antigens, Ly
- Antineoplastic Agents
- Ly-6C antigen, mouse
- Ly6G antigen, mouse
- Recombinant Proteins
- Granulocyte Colony-Stimulating Factor
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Topics |
- Animals
- Antigens, Ly
(immunology)
- Antineoplastic Agents
(pharmacology)
- Cell Line, Tumor
- Cell Movement
- Female
- Gene Expression Profiling
- Granulocyte Colony-Stimulating Factor
(genetics, pharmacology)
- Granulocytes
(cytology, drug effects, immunology)
- Lung Neoplasms
(pathology)
- Male
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Mice, Nude
- Mice, SCID
- Microarray Analysis
- Neoplasm Metastasis
- Neoplasm Transplantation
- Recombinant Proteins
(genetics, pharmacology)
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