Macrophages are exploited from an innate wound healing response to facilitate cancer metastasis.
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Authors
Muliaditan, Tamara
Caron, Jonathan
Okesola, Mary
Opzoomer, James W
Kosti, Paris
Georgouli, Mirella
Gordon, Peter
Lall, Sharanpreet
Kuzeva, Desislava M
Pedro, Luisa
Shields, Jacqueline D
Gillett, Cheryl E
Diebold, Sandra S
Ng, Tony
Publication Date
2018-07-27Journal Title
Nat Commun
ISSN
2041-1723
Publisher
Springer Science and Business Media LLC
Volume
9
Issue
1
Pages
2951
Language
eng
Type
Article
Physical Medium
Electronic
Metadata
Show full item recordCitation
Muliaditan, T., Caron, J., Okesola, M., Opzoomer, J. W., Kosti, P., Georgouli, M., Gordon, P., et al. (2018). Macrophages are exploited from an innate wound healing response to facilitate cancer metastasis.. Nat Commun, 9 (1), 2951. https://doi.org/10.1038/s41467-018-05346-7
Abstract
Tumour-associated macrophages (TAMs) play an important role in tumour progression, which is facilitated by their ability to respond to environmental cues. Here we report, using murine models of breast cancer, that TAMs expressing fibroblast activation protein alpha (FAP) and haem oxygenase-1 (HO-1), which are also found in human breast cancer, represent a macrophage phenotype similar to that observed during the wound healing response. Importantly, the expression of a wound-like cytokine response within the tumour is clinically associated with poor prognosis in a variety of cancers. We show that co-expression of FAP and HO-1 in macrophages results from an innate early regenerative response driven by IL-6, which both directly regulates HO-1 expression and licenses FAP expression in a skin-like collagen-rich environment. We show that tumours can exploit this response to facilitate transendothelial migration and metastatic spread of the disease, which can be pharmacologically targeted using a clinically relevant HO-1 inhibitor.
Keywords
Cell Line, Tumor, Macrophages, Skin, Animals, Mice, Inbred BALB C, Humans, Mice, Mice, Mutant Strains, Breast Neoplasms, Neoplasm Metastasis, Collagen, Gelatinases, Serine Endopeptidases, Membrane Proteins, Interleukin-6, Cytokines, Prognosis, Wound Healing, Cell Survival, Gene Expression Regulation, Neoplastic, Phenotype, Female, Heme Oxygenase-1, Tumor Microenvironment
Sponsorship
MRC (unknown)
Medical Research Council (MC_UU_12022/5)
Identifiers
External DOI: https://doi.org/10.1038/s41467-018-05346-7
This record's URL: https://www.repository.cam.ac.uk/handle/1810/284694
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