title: Pancreatic stellate cells promote epithelial-mesenchymal transition in pancreatic cancer cells.
abstract: The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression of pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Because epithelial-mesenchymal transition (EMT) plays a critical role in the progression of pancreatic cancer, we hypothesized that PSCs promote EMT in pancreatic cancer cells. Panc-1 and SUIT-2 pancreatic cancer cells were indirectly co-cultured with human PSCs isolated from patients undergoing operation for pancreatic cancer. The expression of epithelial and mesenchymal markers was examined by real-time PCR and immunofluorescent staining. The migration of pancreatic cancer cells was examined by scratch and two-chamber assays. Pancreatic cancer cells co-cultured with PSCs showed loose cell contacts and a scattered, fibroblast-like appearance. The expression of E-cadherin, cytokeratin 19, and membrane-associated β-catenin was decreased, whereas vimentin and Snail (Snai-1) expression was increased more in cancer cells co-cultured with PSCs than in mono-cultured cells. The migration of pancreatic cancer cells was increased by co-culture with PSCs. The PSC-induced decrease of E-cadherin expression was not altered by treatment with anti-TGF-β-neutralizing antibody, excluding a central role of TGF-β in this process. In conclusion, PSCs promoted EMT in pancreatic cancer cells suggesting a novel mechanism by which PSCs contribute to the aggressive behavior of pancreatic cancer cells.
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kikuta
authors.forename: Atsushi
authors.initials: A
authors.lastname: Masamune
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ariga
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Itoh
authors.forename: Shin
authors.initials: S
authors.lastname: Hamada
authors.forename: Kennichi
authors.initials: K
authors.lastname: Satoh
authors.forename: Shinichi
authors.initials: S
authors.lastname: Egawa
authors.forename: Michiaki
authors.initials: M
authors.lastname: Unno
authors.forename: Tooru
authors.initials: T
authors.lastname: Shimosegawa
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology; D014408:Biomarkers, Tumor / Q000032:analysis; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D018920:Coculture Techniques; D058750:Epithelial-Mesenchymal Transition; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D010190:Pancreatic Neoplasms / Q000473:pathology*; D058954:Pancreatic Stellate Cells / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D014408:Biomarkers, Tumor; D015820:Cadherins; D016212:Transforming Growth Factor beta