EMT and Dissemination Precede Pancreatic Tumor Formation

Abstract

Summary 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-tomesenchymal 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 new 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.

Targeting of the P2X7 receptor in pancreatic cancer and stellate cells

“…There are two main theories about how epithelial cells might drive the tumour development. In the classical model it has been proposed that pancreatic ducts undergo a series of pancreatic intraepithelial neoplasias (PanINs), epithelial to mesenchymal transition (EMT) and progression to invasive cancer 5. A number of studies support a different model, which proposes that acinar‐to‐duct metaplasia can give rise to tubular complexes that may occur in parallel and/or progress to PDAC 6, 7.…”

Survival Outcome and EMT Suppression Mediated by a Lectin Domain Interaction of Endo180 and CD147

“…2). EMT has also been closely linked to the early stages of tumor development, following the finding that EMT-associated metastatic dissemination precedes detectable adenocarcinoma formation in glandular tissue (3). This strongly suggests that molecular triggers of EMT in normal epithelial layers should be prioritized as targets for the development of therapeutics that can prevent metastasis and improve cancer survival rates.…”

Les étapes précoces du processus métastatique

“…La dissémination précoce de cellules à l'origine des métastases a également été observée dans les cancers de l'oesophage [12]. La dissémination précoce des cellules tumorales a pu être analysée plus en détail dans plusieurs modèles murins de cancers spontanés (cancer du sein [6], méla-nome uvéal [13], pancréas [14]), où l'on peut suivre le développement de la maladie avant même l'apparition des premiers symptômes cliniques. Dans ces modèles, on détecte des cellules cancéreuses disséminées dans pratiquement tous les tissus dès que la lésion primitive se développe, parfois même à un stade précancéreux (dysplasique).…”