IL-1β inflammatory response driven by primary breast cancer prevents metastasis-initiating cell colonization.

Nat Cell Biol
Authors
Keywords
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-1β (IL-1β)-expressing innate immune cells that infiltrate distant MIC microenvironments. At the metastatic site, IL-1β 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-1β 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.

Year of Publication
2018
Journal
Nat Cell Biol
Volume
20
Issue
9
Pages
1084-1097
Date Published
2018 09
ISSN
1476-4679
DOI
10.1038/s41556-018-0173-5
PubMed ID
30154549
PubMed Central ID
PMC6511979
Links
Grant list
R01 CA166284 / CA / NCI NIH HHS / United States