Project 467080

In 2020, Pancreatic cancer (PC) is the 3rd leading cause of cancer death in Canada, which accounts for 6.4% of total cases. Although the incidence of pancreatic cancer is relatively low compared with other cancer types, it is highly aggressive such that even with early diagnosis, almost all patients eventually develop metastases with poor five-year survival rate. Multiple pancreatic cell types can give rise to PC cells. The predominant cellular origin of PC is the pancreatic acinar cell, the most abundant cell type in the pancreas that functions to produce and secrete various digestive enzymes. Under certain cellular stresses such as cancer-driver mutations, acinar cells can be transformed into PC cells through specific pre-cancerous lesions.Obesity and type 2 diabetes (T2D) are well documented risk factors that are associated with PC, although how they promote PC progression is poorly understood. Excessive circulating insulin, a common symptom shared by obesity and T2D, may explain this association because high fasting insulin level is known to be linked to increased risk of developing cancer. In fact, the Kopp and Johnson labs (UBC) recently found that high insulin levels likely play a positive role in PC initiation, as genetic reduction of insulin level resulted in fewer pre-cancerous lesions in mice. Here, we propose to investigate the exact mechanism behind this observation. We hypothesize that insulin acts directly on acinar cells to enhance PC initiation by promoting the formation of PC pre-cancerous lesions and will test this hypothesis by treating mouse acinar cells with increasing levels of insulin. This study may improve our current understanding of PC development, which could potentially uncover novel effective treatments or prevention strategies for PC.