Muliaditan, T;
Caron, J;
Okesola, M;
Opzoomer, JW;
Kosti, P;
Georgouli, M;
Gordon, P;
... Arnold, JN; + view all
(2018)
Macrophages are exploited from an innate wound healing response to facilitate cancer metastasis.
Nature Communications
, 9
, Article 2951. 10.1038/s41467-018-05346-7.
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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.
| Type: | Article |
|---|---|
| Title: | Macrophages are exploited from an innate wound healing response to facilitate cancer metastasis |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41467-018-05346-7 |
| Publisher version: | https://doi.org/10.1038/s41467-018-05346-7 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/ |
| Keywords: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, FIBROBLAST ACTIVATION PROTEIN, TUMOR-ASSOCIATED MACROPHAGES, BREAST-CANCER, HEME OXYGENASE-1, CARBON-MONOXIDE, ALTERNATIVE ACTIVATION, INFLAMMATORY MONOCYTES, BILIRUBIN PRODUCTION, STROMAL FIBROBLASTS, TIN-MESOPORPHYRIN |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > The Sainsbury Wellcome Centre UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10072421 |
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