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

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

University of Cambridge

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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
Pages (from-to)	1-15
Journal	Nature Communications
Volume	9
Early online date	27 Jul 2018
DOIs	https://doi.org/10.1038/s41467-018-05346-7
Publication status	Published - 27 Jul 2018

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Macrophages are exploited from_MULIADITAN_Accepted3July2018_GOLD VoR (CC BY)Final published version, 5.07 MBLicence: CC BY

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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. (2018). Macrophages are exploited from an innate wound healing response to facilitate cancer metastasis. Nature Communications, 9, 1-15. Article 2951. https://doi.org/10.1038/s41467-018-05346-7

@article{429c2be6f6bc49688a2b3f1e6f127898,

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.",

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

year = "2018",

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doi = "10.1038/s41467-018-05346-7",

language = "English",

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journal = "Nature Communications",

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publisher = "Nature Publishing Group",

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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, J 2018, 'Macrophages are exploited from an innate wound healing response to facilitate cancer metastasis', Nature Communications, vol. 9, 2951, pp. 1-15. https://doi.org/10.1038/s41467-018-05346-7

TY - JOUR

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, Marigoula

AU - Gordon, Peter

AU - Lall, Sharanpreet

AU - Kuzeva, Desislava M.

AU - Pedro, Luisa

AU - Shields, Jacqui D

AU - Gillett, Cheryl E.

AU - Diebold, Sandra S.

AU - Sanz-Moreno, Victoria

AU - Ng, Tony

AU - Hoste, Esther

AU - Arnold, James

PY - 2018/7/27

Y1 - 2018/7/27

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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U2 - 10.1038/s41467-018-05346-7

DO - 10.1038/s41467-018-05346-7

M3 - Article

SN - 2041-1723

VL - 9

SP - 1

EP - 15

JO - Nature Communications

JF - Nature Communications

M1 - 2951

ER -

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

Abstract

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