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Crosstalk with lung epithelial cells regulates Sfrp2-mediated latency in breast cancer dissemination

Montagner, M; Bhome, R; Hooper, S; Chakravarty, P; Qin, X; Sufi, J; Bhargava, A; ... Sahai, E; + view all (2020) Crosstalk with lung epithelial cells regulates Sfrp2-mediated latency in breast cancer dissemination. Nature Cell Biology , 22 pp. 289-296. 10.1038/s41556-020-0474-3. Green open access

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Abstract

The process of metastasis is complex. In breast cancer, there are frequently long time intervals between cells leaving the primary tumour and growth of overt metastases. Reasons for disease indolence and subsequent transition back to aggressive growth include interactions with myeloid and fibroblastic cells in the tumour microenvironment and ongoing immune surveillance. However, the signals that cause actively growing cells to enter an indolent state, thereby enabling them to survive for extended periods of time, are not well understood. Here we reveal how the behaviour of indolent breast cancer cells in the lung is determined by their interactions with alveolar epithelial cells, in particular alveolar type 1 cells. This promotes the formation of fibronectin fibrils by indolent cells that drive integrin-dependent pro-survival signals. Combined in vivo RNA sequencing and drop-out screening identified secreted frizzled-related protein 2 (SFRP2) as a key mediator of this interaction. Sfrp2 is induced in breast cancer cells by signals from lung epithelial cells and promotes fibronectin fibril formation and survival, whereas blockade of Sfrp2 expression reduces the burden of indolent disease.

Type: Article
Title: Crosstalk with lung epithelial cells regulates Sfrp2-mediated latency in breast cancer dissemination
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41556-020-0474-3
Publisher version: https://doi.org/10.1038/s41556-020-0474-3
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Breast cancer, Cancer, Cancer microenvironment, Metastasis
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 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/10111563
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