Tumour - Stroma Signalling in Pancreatic Cancer Event

Abstract: Tumours are complex organs that, in addition to the transformed cancer cells, contain infiltrating host cells. It is widely accepted that infiltrating cells such as fibroblasts and immune cells influence the malignant behaviour of cancer cells. However, the mechanisms whereby stromal cells support cancer cells are currently not clearly defined. Specifically, our understanding of the reciprocal signals that are exchanged between tumour and stromal cells and their interdependencies is not fully appreciated. To address this we have combined cell-specific labeling by isotopomeric amino acids in long-term co-cultures (CTAP, Gauthier et al Nat Methods 2013 and Tape et al MCP 2014) with global proteomics analysis to discern cell signaling at cell-specific resolution in direct co-culture models. Using this approach we have delineated an oncogene-driven signalling axis, whereby cancer cells co-opt stromal cells to elicit reciprocal signals, which engage new signalling pathways in the cancer cells (Tape et al Cell 2016). Importantly, specific tumour cell phenotypes are only observed in co-culture models, suggesting that our biochemical appreciation of cell signaling in complex model systems needs further investigation.