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Nat Commun ; 11(1): 5265, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067432

RESUMO

Pancreatic ductal adenocarcinoma (PDAC), the fourth leading cause of cancer death, has a 5-year survival rate of approximately 7-9%. The ineffectiveness of anti-PDAC therapies is believed to be due to the existence of a subpopulation of tumor cells known as cancer stem cells (CSCs), which are functionally plastic, and have exclusive tumorigenic, chemoresistant and metastatic capacities. Herein, we describe a 2D in vitro system for long-term enrichment of pancreatic CSCs that is amenable to biological and CSC-specific studies. By changing the carbon source from glucose to galactose in vitro, we force PDAC cells to utilize OXPHOS, resulting in enrichment of CSCs defined by increased CSC biomarker and pluripotency gene expression, greater tumorigenic potential, induced but reversible quiescence, increased OXPHOS activity, enhanced invasiveness, and upregulated immune evasion properties. This CSC enrichment method can facilitate the discovery of new CSC-specific hallmarks for future development into targets for PDAC-based therapies.


Assuntos
Carcinoma Ductal Pancreático/imunologia , Evasão da Resposta Imune , Células-Tronco Neoplásicas/imunologia , Neoplasias Pancreáticas/imunologia , Animais , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Feminino , Humanos , Camundongos , Camundongos Nus , Invasividade Neoplásica , Células-Tronco Neoplásicas/metabolismo , Fosforilação Oxidativa , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia
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