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

被引：523

作者：

Kowanetz, Marcin ^{[1
]}

Wu, Xiumin ^{[1
]}

Lee, John ^{[1
]}

Tan, Martha ^{[1
]}

Hagenbeek, Thijs ^{[1
]}

Qu, Xueping ^{[1
]}

Yu, Lanlan ^{[1
]}

Ross, Jed ^{[1
]}

Korsisaari, Nina ^{[1
]}

Cao, Tim ^{[1
]}

Bou-Reslan, Hani ^{[1
]}

Kallop, Dara ^{[1
]}

Weimer, Robby ^{[1
]}

Ludlam, Mary J. C. ^{[1
]}

Kaminker, Joshua S. ^{[1
]}

Modrusan, Zora ^{[1
]}

van Bruggen, Nicholas ^{[1
]}

Peale, Franklin V. ^{[1
]}

Carano, Richard ^{[1
]}

Meng, Y. Gloria ^{[1
]}

Ferrara, Napoleone ^{[1
]}

机构：

[1] Genentech Inc, San Francisco, CA 94080 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 50期

关键词：

breast cancer; myeloid; CSF3; prokineticin; 2; GR-1+CD11B+ MYELOID CELLS; BREAST-CANCER METASTASIS; GROWTH-FACTOR RECEPTOR-1; MOUSE MAMMARY-TUMOR; IMMUNE SUPPRESSION; ANGIOGENESIS; VEGF; BV8; RECRUITMENT; CARCINOMA;

D O I：

10.1073/pnas.1015855107

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：21248 / 21255

页数：8

共 48 条

[1] Matrix metalloproteinase-9 from bone marrow-derived cells contributes to survival but not growth of tumor cells in the lung microenvironment [J].