Unknown,Transcriptomics,Genomics,Proteomics

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SPR509: Lung metastasis


ABSTRACT: Determine gene expression differences between normal, metastatic and non-metastatic mouse lung tissue. 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. 67NR and 4T1mouse breast carcinoma cell lines were injected into fourth mammary fat pad; lung tissue was collected when tumor reached volume of 50mm3. RNA was extracted using Qiagen kit.

ORGANISM(S): Mus musculus

SUBMITTER: Josh Kaminker 

PROVIDER: E-GEOD-62817 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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

Kowanetz Marcin M   Wu Xiumin X   Lee John J   Tan Martha M   Hagenbeek Thijs T   Qu Xueping X   Yu Lanlan L   Ross Jed J   Korsisaari Nina N   Cao Tim T   Bou-Reslan Hani H   Kallop Dara D   Weimer Robby R   Ludlam Mary J C MJ   Kaminker Joshua S JS   Modrusan Zora Z   van Bruggen Nicholas N   Peale Franklin V FV   Carano Richard R   Meng Y Gloria YG   Ferrara Napoleone N  

Proceedings of the National Academy of Sciences of the United States of America 20101116 50


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  ...[more]

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