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Modulating Immune Cells to Prevent Breast Cancer Lung Metastasis

ABSTRACT: Current lack of insight into mechanisms governing breast cancer metastasis has precluded development of curative therapies. Metastasis-initiating cells (MICs) are cancer cells uniquely equipped to establish metastatic outgrowths and are thought to cause recurrence and therapeutic resistance. Using various models of early metastatic disease, we have uncovered mechanisms by which certain primary tumors can prevent MICs from generating secondary tumors. In such cases, the primary tumor elicits a systemic immune response involving IL-1β expressing innate inflammatory cells that infiltrate the distant MIC microenvironment. Elevated IL-1β levels at the metastatic site prevent MICs from generating their highly proliferative E-cadherin-positive epithelial progeny. Thus, when the inherent plasticity of MICs is impeded, robustly growing tumors cannot be established. Ablation of the pro-inflammatory response or IL-1R inhibition relieves the block in differentiation and results in MIC colonization. Our data reveal complex and potentially life-prolonging interactions that occur between primary tumors and disseminated MICs that could be exploited to improve survival of patients at risk for metastatic disease.

ORGANISM(S): Mus musculus

PROVIDER: GSE111157 | GEO | 2018/06/26

REPOSITORIES: GEO

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