Microenvironmental IL1beta promotes breast cancer metastatic colonisation in the bone via activation of Wnt signalling
Alférez, Denis G
Hart, Claire A
Simoes, Bruno M
Howell, Sacha J
Clarke, Robert B
AffiliationBreast Biology Group, Manchester Breast Centre, Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Wilmslow Road, Manchester, M20 4GJ, UK
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AbstractDissemination of tumour cells to the bone marrow is an early event in breast cancer, however cells may lie dormant for many years before bone metastases develop. Treatment for bone metastases is not curative, therefore new adjuvant therapies which prevent the colonisation of disseminated cells into metastatic lesions are required. There is evidence that cancer stem cells (CSCs) within breast tumours are capable of metastasis, but the mechanism by which these colonise bone is unknown. Here, we establish that bone marrow-derived IL1? stimulates breast cancer cell colonisation in the bone by inducing intracellular NFkB and CREB signalling in breast cancer cells, leading to autocrine Wnt signalling and CSC colony formation. Importantly, we show that inhibition of this pathway prevents both CSC colony formation in the bone environment, and bone metastasis. These findings establish that targeting IL1?-NFKB/CREB-Wnt signalling should be considered for adjuvant therapy to prevent breast cancer bone metastasis.
CitationEyre R, Alferez DG, Santiago-Gomez A, Spence K, McConnell JC, Hart C, et al. Microenvironmental IL1beta promotes breast cancer metastatic colonisation in the bone via activation of Wnt signalling. Nat Commun. 2019;10(1):5016.