Macrophages are exploited from an innate wound healing response to facilitate cancer metastasis

Tamara Muliaditan; Jonathan Caron; Mary Okesola; James W. Opzoomer; Paris Kosti; Mirella Georgouli; Peter Gordon; Sharanpreet Lall; Desislava M. Kuzeva; Luisa Pedro; Jacqueline D. Shields; Cheryl E. Gillett; Sandra S. Diebold; Victoria Sanz-Moreno; Tony Ng; Esther Hoste; James N. Arnold

doi:10.1038/s41467-018-05346-7

Macrophages are exploited from an innate wound healing response to facilitate cancer metastasis

Tamara Muliaditan
, Jonathan Caron
, Mary Okesola
, James W. Opzoomer
, Paris Kosti
, Mirella Georgouli
, Peter Gordon
, Sharanpreet Lall
, Desislava M. Kuzeva
, Luisa Pedro
, Jacqueline D. Shields
, Cheryl E. Gillett
, Sandra S. Diebold
, Victoria Sanz-Moreno
, Tony Ng
, Esther Hoste
, James N. Arnold^*

^*Corresponding author for this work

Strathclyde Institute Of Pharmacy And Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

114 Citations (Scopus)

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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.

Original language	English
Article number	2951
Journal	Nature Communications
Volume	9
Issue number	1
Early online date	27 Jul 2018
DOIs	https://doi.org/10.1038/s41467-018-05346-7
Publication status	Published - 1 Dec 2018

Funding

This work was funded by a grant from the European Research Council (335326). E.H. is supported by an FWO postdoctoral fellowship, and P.G. was supported by a grant from the Wellcome Trust (101529/Z/13/2). V.S.M. is supported by Cancer Research UK grants C33043/A12065 and C33043/A24478. T.M. would like to thank KCL for the George Brownlee Award, which supported this work. J.W.O. and P.K. are supported by the UK Medical Research Council (MR/N013700/1) and are KCL members of the MRC Doctoral Training Partnership in Biomedical Sciences. The research was supported by the Experimental Cancer Medicine Centre at King’s College London and the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

macrophages
breast cancer
cytokine response

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10.1038/s41467-018-05346-7Licence: CC BY 4.0

Macrophages are exploited from an innate wound healing response to facilitate cancer metastasisFinal published version, 5.07 MBLicence: CC BY 4.0

Cite this

Muliaditan, T., Caron, J., Okesola, M., Opzoomer, J. W., Kosti, P., Georgouli, M., Gordon, P., Lall, S., Kuzeva, D. M., Pedro, L., Shields, J. D., Gillett, C. E., Diebold, S. S., Sanz-Moreno, V., Ng, T., Hoste, E., & Arnold, J. N. (2018). Macrophages are exploited from an innate wound healing response to facilitate cancer metastasis. Nature Communications, 9(1), Article 2951. https://doi.org/10.1038/s41467-018-05346-7

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title = "Macrophages are exploited from an innate wound healing response to facilitate cancer metastasis",

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 = "macrophages, breast cancer, cytokine response",

author = "Tamara Muliaditan and Jonathan Caron and Mary Okesola and Opzoomer, \{James W.\} and Paris Kosti and Mirella Georgouli and Peter Gordon and Sharanpreet Lall and Kuzeva, \{Desislava M.\} and Luisa Pedro and Shields, \{Jacqueline D.\} and Gillett, \{Cheryl E.\} and Diebold, \{Sandra S.\} and Victoria Sanz-Moreno and Tony Ng and Esther Hoste and Arnold, \{James N.\}",

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Muliaditan, T, Caron, J, Okesola, M, Opzoomer, JW, Kosti, P, Georgouli, M, Gordon, P, Lall, S, Kuzeva, DM, Pedro, L, Shields, JD, Gillett, CE, Diebold, SS, Sanz-Moreno, V, Ng, T, Hoste, E & Arnold, JN 2018, 'Macrophages are exploited from an innate wound healing response to facilitate cancer metastasis', Nature Communications, vol. 9, no. 1, 2951. https://doi.org/10.1038/s41467-018-05346-7

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T1 - Macrophages are exploited from an innate wound healing response to facilitate cancer metastasis

AU - Muliaditan, Tamara

AU - Caron, Jonathan

AU - Okesola, Mary

AU - Opzoomer, James W.

AU - Kosti, Paris

AU - Georgouli, Mirella

AU - Gordon, Peter

AU - Lall, Sharanpreet

AU - Kuzeva, Desislava M.

AU - Pedro, Luisa

AU - Shields, Jacqueline D.

AU - Gillett, Cheryl E.

AU - Diebold, Sandra S.

AU - Sanz-Moreno, Victoria

AU - Ng, Tony

AU - Hoste, Esther

AU - Arnold, James N.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

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KW - cytokine response

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Macrophages are exploited from an innate wound healing response to facilitate cancer metastasis

Abstract

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UN SDGs

Keywords

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