Granulocyte-colony stimulating factor promotes lung metastasis through mobilization of Ly6G+Ly6C+ granulocytes
Open accessAbstract
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.
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Blocking antibodies against G-CSF can reduce metastases in mice.
“Blocking antibodies against G-CSF reduced cancer cell-induced NET formation in our study and can reduce metastases in mice (34, 35).”
From Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps (2016) · cites this paper as [35]
4T1 cells and C3(1)-Tag tumors express high levels of G-CSF.
“Both 4T1 cells and C3(1)-Tag tumors express high levels of G-CSF (22, 35), and they are both models of triple-negative breast cancer.”
From Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps (2016) · cites this paper as [35]
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- Authors
- Kowanetz, M., Wu, X., Lee, J., Tan, M., Hagenbeek, T., Qu, X., Yu, L., Ross, J., Korsisaari, N., Cao, T., Bou-Reslan, H., Kallop, D., Weimer, R., Ludlam, M. J. C., Kaminker, J. S., Modrusan, Z., van Bruggen, N., Peale, F. V., Carano, R., Meng, Y. G., & Ferrara, N.
- Affiliations
- Genentech (US)
- Genentech Inc., South San Francisco, CA 94080
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-11-16
- Volume
- 107
- Issue
- 50
- Pages
- 21248-21255
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3003076
- OpenAlex
- W2064315259
- Cited by
- 663
- References
- 50
- Citations by year
- 2026: 21 · 2025: 29 · 2024: 43 · 2023: 59 · 2022: 65 · 2021: 63 · 2020: 61 · 2019: 48 · 2018: 46 · 2017: 54 · 2016: 45 · 2015: 41 · 2014: 26 · 2013: 29 · 2012: 24
- FWCI
- 9.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Barbara Ann Karmanos Cancer Institute
- Genentech
- Topics
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- granulocyte colony-stimulating factor, lung metastasis, Bv8, prokineticin receptor 1, pre-metastatic niche, tumor cell migration, granulocyte mobilization, tumor angiogenesis, myeloid cell recruitment
- MeSH terms
- Animals, Antigens, Ly, Antineoplastic Agents, Cell Movement, Female, Granulocytes, Lung Neoplasms, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Nude, Neoplasm Metastasis, Neoplasm Transplantation, Recombinant Proteins, Granulocyte Colony-Stimulating Factor, Mice, SCID, Gene Expression Profiling, Cell Line, Tumor, Microarray Analysis, Mice
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