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

Valle, S. ; Alcalá, S. ; Martin-Hijano, L. ; Cabezas-Sáinz, P. ; Navarro, D. ; Muñoz, E.R. ; Yuste, L. ; Tiwary, K. ; Walter, K. ; Ruiz-Cañas, L. ; Alonso-Nocelo, M. ; Rubiolo, J.A. ; González-Arnay, E. ; Heeschen, C. ; Garcia-Bermejo, L. ; Hermann, P.C. ; Sánchez, L. ; Sancho, P. ; Fernández-Moreno, M.Á. ; Sainz, B. ; , Jr.

Resumen: 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.

Idioma: Inglés

DOI: 10.1038/s41467-020-18954-z

Año: 2020

Publicado en: Nature Communications 11, 1 (2020), 5265 [19 pp]
ISSN: 2041-1723

Factor impacto JCR: 14.919 (2020)

Categ. JCR: MULTIDISCIPLINARY SCIENCES rank: 4 / 73 = 0.055 (2020) - Q1 - T1

Factor impacto SCIMAGO: 5.559 - Biochemistry, Genetics and Molecular Biology (miscellaneous) (Q1) - Physics and Astronomy (miscellaneous) (Q1) - Chemistry (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/ES/FEDER/Una manera de hacer Europa
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI16-00789
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI18-00757
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI18-01347
Financiación: info:eu-repo/grantAgreement/ES/MINECO/RYC-2012-12104

Tipo y forma: Article (Published version)