Background: Pancreatic ductal adenocarcinoma (PDAC) is charac- terised by an abundant stroma composed predominantly of activated fi- broblasts (CAFs) and dense extracellular matrix (ECM). Tumour cell growth and ECM modifications generate forces named “solid stress” documented to promote tumour progression. While it is recognised that these forces also result in compression of surrounding healthy tissue, their impact on the biology of adjacent normal cells, especially normal fibroblasts (Pancreatic Stellate Cells, PSCs) remain poorly described. Methods & Results: In order to mimic the mechanical force trans- mitted by the tumour to the surrounding healthy tissue, we have devel- oped a 2D model in which a pad is added on the top of a monolayer of PSCs. We show that a low pressure (85 Pa) induces a strong expression of at least three of the main markers of activated fibroblasts. This phenomenon is associated with the activation of the mechanosensor FAK, drastic changes in cell morphology and a rearrangement of the mitochondrial network. Importantly, the mechanically-induced activation of the fibroblasts is a stable phenotype that persists for at least seven days after removing the pressure. In addition, fibroblasts submitted to pressure acquire the ca- pacity to produce and deposit ECM, such as collagen I, a hallmark of myofibroblastic CAFs. This matrix secreted by the mechanically-activated fibroblasts promotes the induction of the epithelial-to-mesenchymal transition in tumour cells. We are currently developing an original 3D device, allowing the application of a quantifiable and homogeneous pressure on cells embedded in a gelatin methacrylate (GelMA) hydrogel, to verify our results in a context more relevant to the pathology. This device, compatible with a wide range of techniques (IF, WB, RNAseq, live imaging…) will enable us to deeply characterise the impact of tumour-generated pressure on normal adjacent pancreatic fibroblasts Conclusion: We obtained the proof of concept in 2D, and will verify it in 3D, that solid stress activates PSCs in a durable manner and confer them protumoural properties that most likely will support and favour tumoural progression.