title: Pancreatic ductal adenocarcinoma cell lines display a plastic ability to bi‑directionally convert into cancer stem cells.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed when metastatic events have occurred. Cancer stem cells (CSCs) play an important role in tumor initiation, metastasis, chemoresistance and relapse. A growing number of studies have suggested that CSCs exist in a dynamic equilibrium with more differentiated cancer cells via a bi‑directional regeneration that is dependent on the environmental stimuli. In this investigation, we obtain, by using a selective medium, PDAC CSCs from five out of nine PDAC cell lines, endowed with different tumorsphere‑forming ability. PDAC CSCs were generally more resistant to the action of five anticancer drugs than parental cell lines and were characterized by an increased expression of EpCAM and CD44v6, typical stem cell surface markers, and a decreased expression of E‑cadherin, the main marker of the epithelial state. PDAC CSCs were able to re‑differentiate into parental cells once cultured in parental growth condition, as demonstrated by re‑acquisition of the epithelial morphology, the decreased expression levels of EpCAM and CD44v6 and the increased sensitivity to anticancer drugs. Finally, PDAC CSCs injected into nude mice developed a larger subcutaneous tumor mass and showed a higher metastatic activity compared to parental cells. The present study demonstrates the ability to obtain CSCs from several PDAC cell lines and that these cells are differentially resistant to various anticancer agents. This variability renders them a model of great importance to deeply understand pancreatic adenocarcinoma biology, to discover new biomarkers and to screen new therapeutic compounds.
authors.affiliation: Department of Life and Reproduction Sciences, Section of Biochemistry, University of Verona, Verona, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Dalla Pozza
authors.affiliation: Department of Life and Reproduction Sciences, Section of Biochemistry, University of Verona, Verona, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Dando
authors.affiliation: Department of Life and Reproduction Sciences, Section of Biochemistry, University of Verona, Verona, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Biondani
authors.affiliation: Department of Biotechnology, University of Verona, Verona, Italy.
authors.forename: Jessica
authors.initials: J
authors.lastname: Brandi
authors.affiliation: Department of Life and Reproduction Sciences, Section of Biochemistry, University of Verona, Verona, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Costanzo
authors.affiliation: Applied Research on Cancer Network (ARC‑NET) and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Zoratti
authors.affiliation: Applied Research on Cancer Network (ARC‑NET) and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.affiliation: Department of Computer Science, University of Verona, Verona, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Boschi
authors.affiliation: Department of Medicine, Oncology Unit, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Melisi
authors.affiliation: Department of Biotechnology, University of Verona, Verona, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cecconi
authors.affiliation: Applied Research on Cancer Network (ARC‑NET) and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Scupoli
authors.affiliation: Applied Research on Cancer Network (ARC‑NET) and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Scarpa
authors.affiliation: Department of Life and Reproduction Sciences, Section of Biochemistry, University of Verona, Verona, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Palmieri
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D054337:Cell Dedifferentiation / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000473:pathology / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology
chemical_list: D014408:Biomarkers, Tumor