Granulocyte-colony stimulating factor promotes lung metastasis through mobilization of Ly6G+Ly6C+ granulocytes
| Autor: | Jed Ross, Thijs J. Hagenbeek, Tim C. Cao, Lanlan Yu, Mary J. C. Ludlam, Robby M. Weimer, Franklin Peale, Napoleone Ferrara, Xueping Qu, Marcin Kowanetz, Nina Korsisaari, Nicholas van Bruggen, Zora Modrusan, John G. Lee, Xiumin Wu, Y. Gloria Meng, Joshua S. Kaminker, Hani Bou-Reslan, Dara Y. Kallop, Richard A.D. Carano, Martha Tan |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Male
Lung Neoplasms Angiogenesis Mice Nude Antineoplastic Agents Mice SCID Biology Metastasis Mice Cell Movement Cell Line Tumor Granulocyte Colony-Stimulating Factor medicine Animals Antigens Ly Neoplasm Metastasis Receptor Mice Inbred BALB C Multidisciplinary Gene Expression Profiling Biological Sciences medicine.disease Microarray Analysis Prokineticin Recombinant Proteins Granulocyte colony-stimulating factor Transplantation Mice Inbred C57BL Cell culture Immunology Cancer research Female Neoplasm Transplantation Homing (hematopoietic) Granulocytes |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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