title: Impact by pancreatic stellate cells on epithelial-mesenchymal transition and pancreatic cancer cell invasion: Adding a third dimension in vitro.
abstract: Pancreatic cancer is associated with a highly abundant stroma and low-grade inflammation. In the local tumour microenvironment, elevated glucose levels, the presence of tumour-associated stellate cells and macrophages are hypothesised to promote the tumour progression and invasion. The present study investigated the influence by the microenvironment on pancreatic cancer cell invasion in vitro. After co-culture with tumour-associated pancreatic stellate cells (TPSCs), pancreatic cancer cells displayed up to 8-fold reduction in levels of epithelial-mesenchymal transition (EMT) markers E-cadherin and ZO-1, while β-catenin and vimentin levels were increased. A 3D organotypic model showed that TPSCs stimulated pancreatic cancer cell invasion, both as single cell (PANC-1) and cohort (MIAPaCa-2) invasion. The combined presence of TPSCs and M2-like macrophages induced invasion of the non-invasive BxPC-3 cells. High glucose conditions further enhanced changes in EMT markers as well as the cancer cell invasion. In summary, co-culture with TPSCs induced molecular changes associated with EMT in pancreatic cancer cells, regardless of differentiation status, and the organotypic model demonstrated the influence of microenvironmental factors, such as glucose, stellate cells and macrophages, on pancreatic cancer cell invasion.
authors.affiliation: Lund University and Skåne University Hospital, Department of Clinical Sciences Lund, Division of Surgery, Lund, Sweden; Lund University and Skåne University Hospital, Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund, Sweden. Electronic address: Emelie.karnevi@med.lu.se.
authors.forename: Emelie
authors.initials: E
authors.lastname: Karnevi
authors.affiliation: Lund University and Skåne University Hospital, Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund, Sweden. Electronic address: Ann.rosendahl@med.lu.se.
authors.forename: Ann H
authors.initials: AH
authors.lastname: Rosendahl
authors.affiliation: Lund University and Skåne University Hospital, Department of Clinical Sciences Lund, Division of Surgery, Lund, Sweden. Electronic address: katarzyna.said_hilmersson@med.lu.se.
authors.forename: Katarzyna Said
authors.initials: KS
authors.lastname: Hilmersson
authors.affiliation: University of Bristol, School of Clinical Sciences, Children's Renal Unit and Academic Renal Unit, Bristol, UK. Electronic address: m.saleem@bristol.ac.uk.
authors.forename: Moin A
authors.initials: MA
authors.lastname: Saleem
authors.affiliation: Lund University and Skåne University Hospital, Department of Clinical Sciences Lund, Division of Surgery, Lund, Sweden. Electronic address: roland.andersson@med.lu.se.
authors.forename: Roland
authors.initials: R
authors.lastname: Andersson
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D058954:Pancreatic Stellate Cells / Q000378:metabolism / Q000473:pathology*; D014746:Vimentin / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D014746:Vimentin
keywords: 3D organotypic model; Epithelial-mesenchymal transition; Invasion; Macrophages; Pancreatic cancer; Pancreatic stellate cells