Exploiting oxidative phosphorylation to promote the stem and immunoevasive properties of pancreatic cancer stem cells

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 functi...

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Detalles Bibliográficos
Autores: Valle, Sandra, Alcalá, Sonia, Martin-Hijano, Laura, Cabezas-Sáinz, Pablo, Navarro, Diego, Muñoz, Edurne Ramos, Yuste, Lourdes, Tiwary, Kanishka, Walter, Karolin, Ruiz-Cañas, Laura, Alonso-Nocelo, Marta, Rubiolo, Juan A., González-Arnay, Emilio, Heeschen, Christopher, Garcia-Bermejo, Laura, Hermann, Patrick C., Sánchez, Laura, Sancho, Patricia, Fernández Moreno, Miguel Ángel, Sainz, Bruno
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/698410
Acceso en línea:http://hdl.handle.net/10486/698410
https://dx.doi.org/10.1038/s41467-020-18954-z
Access Level:acceso abierto
Palabra clave:Cell culture
Cancer stem cells
Pancreatic ductal adenocarcinoma (PDAC)
Biología y Biomedicina / Biología
Descripción
Sumario: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

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