| First Author | Castaño Z | Year | 2018 |
| Journal | Nat Cell Biol | Volume | 20 |
| Issue | 9 | Pages | 1084-1097 |
| PubMed ID | 30154549 | Mgi Jnum | J:268126 |
| Mgi Id | MGI:6271061 | Doi | 10.1038/s41556-018-0173-5 |
| Citation | Castano Z, et al. (2018) IL-1beta inflammatory response driven by primary breast cancer prevents metastasis-initiating cell colonization. Nat Cell Biol 20(9):1084-1097 |
| abstractText | 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-1beta (IL-1beta)-expressing innate immune cells that infiltrate distant MIC microenvironments. At the metastatic site, IL-1beta 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-1beta 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. |
