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

Kowanetz, Marcin ; Wu, Xiumin ; Lee, John ; Tan, Martha ; Hagenbeek, Thijs ; Qu, Xueping ; Yu, Lanlan ; Ross, Jed ; Korsisaari, Nina ; Cao, Tim ; Bou-Reslan, Hani ; Kallop, Dara ; Weimer, Robby ; Ludlam, Mary J. C. ; Kaminker, Joshua S. ; Modrusan, Zora ; van Bruggen, Nicholas ; Peale, Franklin V. ; Carano, Richard ; Meng, Y. Gloria ; Ferrara, Napoleone

Proceedings of the National Academy of Sciences - PNAS, 2010-12, Vol.107 (50), p.21248-21255 [Periódico revisado por pares]

United States: National Academy of Sciences

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Título:
Granulocyte-colony stimulating factor promotes lung metastasis through mobilization of Ly6G+Ly6C+ granulocytes
Autor: Kowanetz, Marcin ; Wu, Xiumin ; Lee, John ; Tan, Martha ; Hagenbeek, Thijs ; Qu, Xueping ; Yu, Lanlan ; Ross, Jed ; Korsisaari, Nina ; Cao, Tim ; Bou-Reslan, Hani ; Kallop, Dara ; Weimer, Robby ; Ludlam, Mary J. C. ; Kaminker, Joshua S. ; Modrusan, Zora ; van Bruggen, Nicholas ; Peale, Franklin V. ; Carano, Richard ; Meng, Y. Gloria ; Ferrara, Napoleone
Assuntos: Angiogenesis ; Animals ; Antibodies ; Antigens, Ly - immunology ; Antineoplastic Agents - pharmacology ; Biological Sciences ; Bone marrow cells ; Cancer ; Cell adhesion & migration ; Cell Line, Tumor ; Cell lines ; Cell Movement ; Female ; Gene expression ; Gene Expression Profiling ; Granulocyte Colony-Stimulating Factor - genetics ; Granulocyte Colony-Stimulating Factor - pharmacology ; Granulocytes ; Granulocytes - cytology ; Granulocytes - drug effects ; Granulocytes - immunology ; Leukocytes ; Lung Neoplasms - pathology ; Lungs ; Male ; Metastasis ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Nude ; Mice, SCID ; Microarray Analysis ; Myeloid cells ; Neoplasm Metastasis ; Neoplasm Transplantation ; Proteins ; Recombinant Proteins - genetics ; Recombinant Proteins - pharmacology ; Studies ; Tumors
É parte de: Proceedings of the National Academy of Sciences - PNAS, 2010-12, Vol.107 (50), p.21248-21255
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
Contributed by Napoleone Ferrara, October 21, 2010 (sent for review September 26, 2010)
Author contributions: M.K. and N.F. designed research; M.K., X.W., J.L., M.T., T.H., X.Q., L.Y., J.R., N.K., T.C., H.B.-R., and D.K. performed research; L.Y. contributed new reagents/analytic tools; M.K., T.C., H.B.-R., D.K., R.W., M.J.C.L., J.S.K., Z.M., N.v.B., F.V.P., R.C., and Y.G.M. analyzed data; and M.K. and N.F. wrote the paper.
Descrição: 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.
Editor: United States: National Academy of Sciences
Idioma: Inglês

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

United States: National Academy of Sciences

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