TY - JOUR
T1 - Exploiting oxidative phosphorylation to promote the stem and immunoevasive properties of pancreatic cancer stem cells
AU - Valle, Sandra
AU - Alcalá, Sonia
AU - Martin-Hijano, Laura
AU - Cabezas-Sáinz, Pablo
AU - Navarro, Diego
AU - Muñoz, Edurne Ramos
AU - Yuste, Lourdes
AU - Tiwary, Kanishka
AU - Walter, Karolin
AU - Ruiz-Cañas, Laura
AU - Alonso-Nocelo, Marta
AU - Rubiolo, Juan A.
AU - González-Arnay, Emilio
AU - Heeschen, Christopher
AU - Garcia-Bermejo, Laura
AU - Hermann, Patrick C.
AU - Sánchez, Laura
AU - Sancho, Patricia
AU - Fernández-Moreno, Miguel Ángel
AU - Sainz, Bruno
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85092640684
U2 - 10.1038/s41467-020-18954-z
DO - 10.1038/s41467-020-18954-z
M3 - Article
C2 - 33067432
AN - SCOPUS:85092640684
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5265
ER -