IL-1β inflammatory response driven by primary breast cancer prevents metastasis-initiating cell colonization
- 1 September 2018
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 20 (9), 1084-+
- https://doi.org/10.1038/s41556-018-0173-5
Abstract
Lack of insight into mechanisms governing breast cancer metastasis has precluded the development of curative therapies. Metastasis-initiating cancer cells (MICs) are uniquely equipped to establish metastases, causing recurrence and therapeutic resistance. Using various metastasis models, we discovered that certain primary tumours elicit a systemic inflammatory response involving interleukin-1 beta (IL-1 beta)-expressing innate immune cells that infiltrate distant MIC microenvironments. At the metastatic site, IL-1 beta maintains MICs in a ZEB1-positive differentiation state, preventing MICs from generating highly proliferative E-cadherin-positive progeny. Thus, when the inherent plasticity of MICs is impeded, overt metastases cannot be established. Ablation of the pro-inflammatory response or inhibition of the IL-1 receptor relieves the differentiation block and results in metastatic colonization. Among patients with lymph node-positive breast cancer, high primary tumour IL-1 beta expression is associated with better overall survival and distant metastasis-free survival. Our data reveal complex interactions that occur between primary tumours and disseminated MICs that could be exploited to improve patient survival.This publication has 73 references indexed in Scilit:
- STAR: ultrafast universal RNA-seq alignerBioinformatics, 2012
- clusterProfiler: an R Package for Comparing Biological Themes Among Gene ClustersOMICS: A Journal of Integrative Biology, 2012
- Tumor Entrained Neutrophils Inhibit Seeding in the Premetastatic LungCancer Cell, 2011
- Normal and neoplastic nonstem cells can spontaneously convert to a stem-like stateProceedings of the National Academy of Sciences of the United States of America, 2011
- Macrophages induce COX-2 expression in breast cancer cells: role of IL-1β autoamplificationCarcinogenesis: Integrative Cancer Research, 2011
- Why not treat human cancer with interleukin-1 blockade?Cancer and Metastasis Reviews, 2010
- Monocyte Chemoattractant Protein-1 (MCP-1): An OverviewJournal of Interferon & Cytokine Research, 2009
- Alternative activation of macrophagesNature Reviews Immunology, 2003
- Dissemination and growth of cancer cells in metastatic sitesNature Reviews Cancer, 2002
- Multistep Nature of Metastatic Inefficiency: Dormancy of Solitary Cells after Successful Extravasation and Limited Survival of Early MicrometastasesThe American Journal of Pathology, 1998