Granulocyte-colony stimulating factor promotes lung metastasis through mobilization of Ly6G+Ly6C+ granulocytes.
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| 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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