Pre-clinical phaeochromocytoma and paraganglioma models: Cell lines, animal models, and a human primary culture model

Katharina Wang; Alessa Fischer; Umberto Maccio; Constanze Hantel; Felix Beuschlein; Ashley B Grossman; Karel Pacak; Svenja Nölting

doi:10.1016/j.beem.2024.101913

Pre-clinical phaeochromocytoma and paraganglioma models: Cell lines, animal models, and a human primary culture model

Best Pract Res Clin Endocrinol Metab. 2024 Dec;38(6):101913. doi: 10.1016/j.beem.2024.101913. Epub 2024 Jul 4.

Authors

Katharina Wang¹, Alessa Fischer², Umberto Maccio³, Constanze Hantel⁴, Felix Beuschlein⁵, Ashley B Grossman⁶, Karel Pacak⁷, Svenja Nölting⁸

Affiliations

¹ Department of Internal Medicine IV, LMU University Hospital, LMU Munich, 80336 Munich, Germany.
² Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), CH-8091 Zurich, Switzerland.
³ Department of Pathology and Molecular Pathology, University Hospital Zurich, CH-8091 Zurich, Switzerland.
⁴ Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), CH-8091 Zurich, Switzerland; Department of Internal Medicine III, University Hospital Carl Gustav Carus Dresden, 01307 Dresden, Germany.
⁵ Department of Internal Medicine IV, LMU University Hospital, LMU Munich, 80336 Munich, Germany; Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), CH-8091 Zurich, Switzerland; The LOOP Zurich - Medical Research Center, 8044 Zurich, Switzerland.
⁶ Green Templeton College, University of Oxford, Oxford OX2 6HG, UK; NET Unit, ENETS Centre of Excellence, Royal Free Hospital, London NW3 2QG, UK.
⁷ Eunice Kennedy Shriver NICHD, NIH, Bethesda, MD 20892, USA.
⁸ Department of Internal Medicine IV, LMU University Hospital, LMU Munich, 80336 Munich, Germany; Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), CH-8091 Zurich, Switzerland. Electronic address: [email protected].

PMID: 38972796
DOI: 10.1016/j.beem.2024.101913

Abstract

While the establishment of human phaeochromocytoma and paraganglioma (PPGL) cell lines has proven to be particularly difficult over several decades of research, there are other reliable pre-clinical PPGL models currently available. This review provides a summary of these models, together with our recently established personalised drug screening platform using patient-derived PPGL primary cultures. Such currently available PPGL models include murine and rat PPGL cell lines, of which only one cell line (PC12) is publicly accessible through a cell repository, and PPGL animal models, of which the patient-derived xenograft models are promising but complex to establish. We have developed next-generation implementation of human PPGL primary cultures, enabling reliable and personalised drug screening and an individualised analysis of tumour drug responsivity based on the tumour's unique genetic, biochemical, immunohistochemical and clinical profile. Overall, reliable PPGL models, including patient-derived primary culture models, are essential to advance pre-clinical research in the field of PPGLs.

Keywords: animal model; cell line; paraganglioma; patient-derived primary culture; personalized drug testing; pheochromocytoma.

Publication types

Review

MeSH terms

Adrenal Gland Neoplasms* / pathology
Animals
Cell Line, Tumor
Disease Models, Animal
Humans
Mice
Paraganglioma* / genetics
Paraganglioma* / pathology
Pheochromocytoma* / genetics
Pheochromocytoma* / pathology
Primary Cell Culture / methods
Rats