Journal article
Mutant KRAS promotes malignant pleural effusion formation
- Abstract:
- Malignant pleural effusion (MPE) is the lethal consequence of various human cancers metastatic to the pleural cavity. However, the mechanisms responsible for the development of MPE are still obscure. Here we show that mutant KRAS is important for MPE induction in mice. Pleural disseminated, mutant KRAS bearing tumour cells upregulate and systemically release chemokine ligand 2 (CCL2) into the bloodstream to mobilize myeloid cells from the host bone marrow to the pleural space via the spleen. These cells promote MPE formation, as indicated by splenectomy and splenocyte restoration experiments. In addition, KRAS mutations are frequently detected in human MPE and cell lines isolated thereof, but are often lost during automated analyses, as indicated by manual versus automated examination of Sanger sequencing traces. Finally, the novel KRAS inhibitor deltarasin and a monoclonal antibody directed against CCL2 are equally effective against an experimental mouse model of MPE, a result that holds promise for future efficient therapies against the human condition.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.2MB, Terms of use)
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- Publisher copy:
- 10.1038/ncomms15205
Authors
- Publisher:
- Nature Publishing Group
- Journal:
- Nature Communications More from this journal
- Volume:
- 8
- Pages:
- 15205
- Publication date:
- 2017-05-01
- Acceptance date:
- 2017-03-08
- DOI:
- ISSN:
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2041-1723
- Keywords:
- Pubs id:
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pubs:810123
- UUID:
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uuid:e50793ec-1b8b-4e38-8a44-71c4bdf51c2e
- Local pid:
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pubs:810123
- Source identifiers:
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810123
- Deposit date:
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2017-12-21
Terms of use
- Copyright holder:
- Kanellakis et al
- Copyright date:
- 2017
- Notes:
- © The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
- Licence:
- CC Attribution (CC BY)
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