NLRP3 inflammasome in fibroblasts links tissue damage with inflammation in breast cancer progression and metastasis.

ABSTRACT: Cancer-Associated Fibroblasts (CAFs) were shown to orchestrate tumour-promoting inflammation in multiple malignancies, including breast cancer. However, the molecular pathways that govern the inflammatory role of CAFs are poorly characterised. In this study we found that fibroblasts sense damage-associated molecular patterns (DAMPs), and in response activate the NLRP3 inflammasome pathway, resulting in instigation of pro-inflammatory signalling and secretion of IL-1β. This upregulation was evident in CAFs in mouse and in human breast carcinomas. Moreover, CAF-derived inflammasome signalling facilitated tumour growth and metastasis, which was attenuated when NLRP3 or IL-1β were specifically ablated. Functionally, CAF-derived inflammasome promoted tumour progression and metastasis by modulat

SUBMITTER: Ershaid N 

PROVIDER: S-EPMC6763472 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature