Introduction
Many studies have focused heavily on the role of the pro-inflammatory cytokine interleukin (IL)-6 in the regulation of the dynamic cross-talk between immune cells, stromal cells and neighbouring cancer cells in the tumour microenvironment. The progression of pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma (PDAC) has recently been linked to IL-6 mediated STAT3 activation in mouse models.We are interested in the related cytokine, IL-11, a member of the IL-6 family of cytokines that also activates the pro-tumorigenic STAT3 signalling cascade.
Methods
We have utilised the Pdx1-Cre;LSL-KrasG12D/+;LSL-p53R172H/+;Rosa26LSL-YFP(PKTY) mouse model of PDAC to genetically dissect the role of IL-11 in cancer onset and metastatic progression. Fluorescence activated cell sorting of different cell populations within the tumour microenvironment of PKTY mice was performed to catalogue the different cellular sources of IL-11. Organoids generated from primary and liver metastases from PKTY mice will be used to generate syngeneic xenografts in mice lacking
IL-11 following tissue specific cre-recombinase expression. These experiments will allow us to further dissect the source of tumour promoting IL-11 in the microenvironment.
Results and conclusions
We provide striking evidence that IL-11, which is elevated in human PDAC, is a potent driver of PDAC progression and metastasis. Our results suggest that a better understanding of the cross-talk between cytokines and the tumour microenvironment will prove critical to the design and success of future cancer therapies.