EMT and Dissemination Precede Pancreatic Tumor Formation
Menée sur un modèle murin pour l'une et sur un modèle numérique pour l'autre, ces deux études suggèrent que, dans le cancer du pancréas, le processus métastatique débute de façon beaucoup plus précoce qu'on ne le pensait jusqu'à présent
Metastasis is the leading cause of cancer-associated death but has been difficult to study because it involves a series of rare, stochastic events. To capture these events, we developed a sensitive method to tag and track pancreatic epithelial cells in a mouse model of pancreatic cancer. Tagged cells invaded and entered the bloodstream unexpectedly early, before frank malignancy could be detected by rigorous histologic analysis; this behavior was widely associated with epithelial-to-mesenchymal transition (EMT). Circulating pancreatic cells maintained a mesenchymal phenotype, exhibited stem cell properties, and seeded the liver. EMT and invasiveness were most abundant at inflammatory foci, and induction of pancreatitis increased the number of circulating pancreatic cells. Conversely, treatment with the immunosuppressive agent dexamethasone abolished dissemination. These results provide insight into the earliest events of cellular invasion in situ and suggest that inflammation enhances cancer progression in part by facilitating EMT and entry into the circulation. º Invading cells exhibit EMT in an autochthonous model of pancreatic cancer º Mutant cells enter the circulation before cancer is found on histology º Circulating pancreatic cells (CPCs) express cancer stem cell-associated markers º Inflammation is necessary and sufficient for EMT, invasion, and dissemination Prior to detectable pancreatic tumor formation, pancreatic cells invade and enter the bloodstream, explaining why many cancer patients develop metastatic disease despite complete removal of small tumors.