Pancreatic ductal adenocarcinoma cell lines display a plastic ability to bi‑directionally convert into cancer stem cells

Dalla Pozza,Elisa; Dando,Ilaria; Biondani,Giulia; Brandi,Jessica; Costanzo,Chiara; Zoratti,Elisa; Fassan,Matteo; Boschi,Federico; Melisi,Davide; Cecconi,Daniela; Scupoli,Maria Teresa; Scarpa,Aldo; Palmieri,Marta

doi:10.3892/ijo.2014.2796

Pancreatic ductal adenocarcinoma cell lines display a plastic ability to bi‑directionally convert into cancer stem cells

Authors:
- Elisa Dalla Pozza
- Ilaria Dando
- Giulia Biondani
- Jessica Brandi
- Chiara Costanzo
- Elisa Zoratti
- Matteo Fassan
- Federico Boschi
- Davide Melisi
- Daniela Cecconi
- Maria Teresa Scupoli
- Aldo Scarpa
- Marta Palmieri
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Affiliations: Department of Life and Reproduction Sciences, Section of Biochemistry, University of Verona, Verona, Italy, Department of Biotechnology, University of Verona, Verona, Italy, Applied Research on Cancer Network (ARC‑NET) and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy, Department of Computer Science, University of Verona, Verona, Italy, Department of Medicine, Oncology Unit, University and Hospital Trust of Verona, Verona, Italy
Published online on: December 12, 2014 https://doi.org/10.3892/ijo.2014.2796
Pages: 1099-1108

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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.

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