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

M Kowanetz, X Wu, J Lee, M Tan… - Proceedings of the …, 2010 - National Acad Sciences
M Kowanetz, X Wu, J Lee, M Tan, T Hagenbeek, X Qu, L Yu, J Ross, N Korsisaari, T Cao…
Proceedings of the National Academy of Sciences, 2010National Acad Sciences
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 …
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.
National Acad Sciences