Treatment of Pheochromocytoma Cells with Recurrent Cycles of Hypoxia: A New Pseudohypoxic In Vitro Model.


Journal

Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052

Informations de publication

Date de publication:
05 02 2022
Historique:
received: 06 12 2021
revised: 26 01 2022
accepted: 03 02 2022
entrez: 15 2 2022
pubmed: 16 2 2022
medline: 1 4 2022
Statut: epublish

Résumé

Continuous activation of hypoxia pathways in pheochromocytomas and paragangliomas (PPGLs) is associated with higher disease aggressiveness, for which effective treatment strategies are still missing. Most of the commonly used in vitro models lack characteristics of these pseudohypoxic tumors, including elevated expression of hypoxia-inducible factor (HIF) 2α. To address this shortcoming, we investigated whether recurrent hypoxia cycles lead to continuous activation of hypoxia pathways under normoxic conditions and whether this pseudohypoxia is associated with increased cellular aggressiveness. Rat pheochromocytoma cells (PC12) were incubated under hypoxia for 24 h every 3-4 days, up to 20 hypoxia-reoxygenation cycles, resulting in PC12 Z20 cells. PC12 Z20 control cells were obtained by synchronous cultivation under normoxia. RNA sequencing revealed upregulation of

Identifiants

pubmed: 35159368
pii: cells11030560
doi: 10.3390/cells11030560
pmc: PMC8834104
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Deutsche Forschungsgemeinschaft
ID : CRC/Transregio 205/2, Project No. 314061271 - TRR205

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Auteurs

Jana Helm (J)

Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.

Stephan Drukewitz (S)

Core Unit for Molecular Tumor Diagnostics (CMTD), National Center for Tumor Diseases (NCT), 01307 Dresden, Germany.
German Cancer Consortium (DKTK), 01307 Dresden, Germany.
German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.

Isabel Poser (I)

Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.

Susan Richter (S)

Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.

Markus Friedemann (M)

Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.

Doreen William (D)

Core Unit for Molecular Tumor Diagnostics (CMTD), National Center for Tumor Diseases (NCT), 01307 Dresden, Germany.
German Cancer Consortium (DKTK), 01307 Dresden, Germany.
German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.

Hermine Mohr (H)

Institute for Diabetes and Cancer, Helmholtz Centre Munich, Ingolstaedter Landstr.1, 85764 Neuherberg, Germany.
Joint Heidelberg-IDC Translational Diabetes Program, Heidelberg University Hospital, 69120 Heidelberg, Germany.

Svenja Nölting (S)

Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ), University of Zurich (UZH), 8091 Zurich, Switzerland.
Department of Medicine IV, University Hospital, LMU Munich, 80336 Munich, Germany.

Mercedes Robledo (M)

Hereditary Endocrine Cancer Group, Spanish National Cancer Research Center, 28029 Madrid, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28029 Madrid, Spain.

Stefan R Bornstein (SR)

Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.

Graeme Eisenhofer (G)

Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.

Nicole Bechmann (N)

Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
German Institute of Human Nutrition Potsdam-Rehbruecke, Department of Experimental Diabetology, 14558 Nuthetal, Germany.
German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.

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