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

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Listed:
  • Sandra Valle

    (Universidad Autónoma de Madrid (UAM) and Instituto de Investigaciones Biomédicas “Alberto Sols” (IIBM), CSIC-UAM
    Chronic Diseases and Cancer Area 3 - Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS))

  • Sonia Alcalá

    (Universidad Autónoma de Madrid (UAM) and Instituto de Investigaciones Biomédicas “Alberto Sols” (IIBM), CSIC-UAM
    Chronic Diseases and Cancer Area 3 - Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS))

  • Laura Martin-Hijano

    (Universidad Autónoma de Madrid (UAM) and Instituto de Investigaciones Biomédicas “Alberto Sols” (IIBM), CSIC-UAM
    Chronic Diseases and Cancer Area 3 - Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS))

  • Pablo Cabezas-Sáinz

    (Universidad de Santiago de Compostela)

  • Diego Navarro

    (Universidad Autónoma de Madrid (UAM) and Instituto de Investigaciones Biomédicas “Alberto Sols” (IIBM), CSIC-UAM
    Chronic Diseases and Cancer Area 3 - Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS))

  • Edurne Ramos Muñoz

    (Biomarkers and Therapeutic Targets Group - IRYCIS)

  • Lourdes Yuste

    (Universidad Autónoma de Madrid (UAM) and Instituto de Investigaciones Biomédicas “Alberto Sols” (IIBM), CSIC-UAM
    Chronic Diseases and Cancer Area 3 - Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS))

  • Kanishka Tiwary

    (Ulm University)

  • Karolin Walter

    (Ulm University)

  • Laura Ruiz-Cañas

    (Universidad Autónoma de Madrid (UAM) and Instituto de Investigaciones Biomédicas “Alberto Sols” (IIBM), CSIC-UAM
    Chronic Diseases and Cancer Area 3 - Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS))

  • Marta Alonso-Nocelo

    (Universidad Autónoma de Madrid (UAM) and Instituto de Investigaciones Biomédicas “Alberto Sols” (IIBM), CSIC-UAM
    Chronic Diseases and Cancer Area 3 - Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS))

  • Juan A. Rubiolo

    (Universidad de Santiago de Compostela)

  • Emilio González-Arnay

    (Universidad Autónoma de Madrid (UAM))

  • Christopher Heeschen

    (Spanish National Cancer Research Centre (CNIO)
    Shanghai Jiao Tong University School of Medicine)

  • Laura Garcia-Bermejo

    (Biomarkers and Therapeutic Targets Group - IRYCIS)

  • Patrick C. Hermann

    (Ulm University)

  • Laura Sánchez

    (Universidad de Santiago de Compostela)

  • Patricia Sancho

    (IIS Aragón)

  • Miguel Ángel Fernández-Moreno

    (Universidad Autónoma de Madrid (UAM) and Instituto de Investigaciones Biomédicas “Alberto Sols” (IIBM), CSIC-UAM
    Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER)
    Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12))

  • Bruno Sainz

    (Universidad Autónoma de Madrid (UAM) and Instituto de Investigaciones Biomédicas “Alberto Sols” (IIBM), CSIC-UAM
    Chronic Diseases and Cancer Area 3 - Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS))

Abstract

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.

Suggested Citation

  • Sandra Valle & Sonia Alcalá & Laura Martin-Hijano & Pablo Cabezas-Sáinz & Diego Navarro & Edurne Ramos Muñoz & Lourdes Yuste & Kanishka Tiwary & Karolin Walter & Laura Ruiz-Cañas & Marta Alonso-Nocelo, 2020. "Exploiting oxidative phosphorylation to promote the stem and immunoevasive properties of pancreatic cancer stem cells," Nature Communications, Nature, vol. 11(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18954-z
    DOI: 10.1038/s41467-020-18954-z
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