ECM production and TIMP1 production in PaSCs. The production of these factors is regulated by fibroblast growth factor 2, TGF-β1, and PDGF. In addition to cytokine-mediated mechanisms, PaSCs also produce a tumour supportive micro-environment through the production of matri-cellular proteins. The up regulation of matri-cellular proteins such as galectin-1, and tenascin-C is present in the stromal tissues of pancreatic cancer and chronic pancreatitis. Matricellular proteins induce proliferation, migration and production of cytokines, ECM and angiogenic responses in PaSCs, which in turn induce cancer cell proliferation. Matri-cellular proteins may therefore directly contribute to the development of pancreatic cancer through stimulating cancer cell activity. The matricellular protein also facilitates a tumour supportive microenvironment through sustained fibrogenic stellate cell activity. A hypoxic environment in tumours influences pancreatic cancer progression. An oxygen deficient environment concomitantly exists not only in cancer cells but also in surrounding pancreatic stellate cells. The cellular response to hypoxia is mediated by the transcription factor HIF-1, which is a heterodimer protein composed of α and β subunits. Hypoxia also stimulates nuclear expression of HIF-1α followed by the production of vascular endothelial growth factor (VEGF) in PaSCs. The induction of HIF-α indicates that PaSCs serves as oxygen sensing cells within the pancreas. PaSCs, endothelial cells and other cells involved in the development of pancreatic fibrosis therefore function in coordination with a low oxygen microenvironment. Ongoing research Treatment of chronic pancreatitis and pancreatic cancer aims to target the major mechanisms involved in both their activation and proliferation. For example, inhibition of the receptors PDGF, TGF-β and angiotensin II in addition to suppression of the intracellular signalling pathways downstream of these receptors is likely to be of therapeutic benefit. In vitro experiments indicate that PaSCs influence the activation and proliferation process for mitogen activated protein kinase (MAPK) pathways, in particular ERK1/2, p38 kinase and JNK. The inhibition of the majority of MAPK pathways leads to a reduction in the activation and proliferation of PaSCs. Anti-fibrosis treatment strategies targeting PaSCs include inhibition of the activation of quiescent PaSCs. Agents such as angiotensin receptor blockers, serine protease inhibitors and adenine dinucleotide phosphate oxidase inhibit the activation and function of PaSCs. Camostat mesilate, an oral protease inhibitor, that is used to treat patients with chronic pancreatitis inhibited the proliferation and MCP-1 production in PaSCs in vitro. The success and effect of anti-fibrosis therapies in pancreatic cancer treatment, however, remains unclear. Rat PaSCs express COX-2 when stimulated