Fas-threshold signalling in MSCs causes tumour progression and metastasis

• DOI: 10.1101/2020.12.02.406918
• Publication Date: 2020-12-04T07:20:14Z
• Authors: Andrea Mohr; Chu Tianyuan; Christopher T. Cl...; Greg N. Brooke; Vladimir B. Teif; Ralf M. Zwacka
• Keywords: Fas ligand; Tumor progression

Abstract Mesenchymal stem cells (MSCs) are part of the tumour microenvironment and have been implicated in progression. We found number MSCs significantly increased tumour-burdened mice driven by Fas-threshold signalling. Consequently, lacking Fas lost their ability to induce metastasis development a pancreatic cancer model. Mixing with led sustained production pro-metastatic cytokines CCL2 IL6 cells. The levels these depended on MSCs, linking Fas-mediated MSC-proliferation capacity promote Furthermore, we discovered that were induced cell-derived IL1. Analysis patient transcriptomic data revealed high FasL expression correlates MSC markers as well tumours. Moreover, both linked elevated specific for monocytes known possess further activities. These results confirm our experimental findings FasL-MSC-IL1-CCL2/IL6 axis highlight role play