title: Pathology of Human Pheochromocytoma and Paraganglioma Xenografts in NSG Mice.
abstract: A major impediment to the development of effective treatments for metastatic or unresectable pheochromocytomas and paragangliomas has been the absence of valid models for pre-clinical testing. Attempts to establish cell lines or xenografts from human pheochromocytomas and paragangliomas have previously been unsuccessful. NOD-scid gamma (NSG) mice are a recently developed strain lacking functional B-cells, T-cells, and NK cells. We report here that xenografts of primary human paragangliomas will take in NSG mice while maintaining their architectural and immunophenotypic characteristics as expressed in the patients. In contrast to grafts of cell lines and of most common types of primary tumors, the growth rate of grafted paragangliomas is very slow, accurately representing the growth rate of most pheochromocytomas and paragangliomas even in metastases in humans. Although the model is therefore technically challenging, primary patient-derived xenografts of paragangliomas in NSG mice provide a potentially valuable new tool that could prove especially valuable for testing treatments aimed at eradicating the small tumor deposits that are often numerous in patients with metastatic paraganglioma.
authors.affiliation: Department of Pathology and Laboratory Medicine, Tufts Medical Center, 800 Washington Street, Boston, MA, 02111, USA. jpowers1@tuftsmedicalcenter.org.
authors.forename: James F
authors.initials: JF
authors.lastname: Powers
authors.affiliation: Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Karel
authors.initials: K
authors.lastname: Pacak
authors.affiliation: Department of Pathology and Laboratory Medicine, Tufts Medical Center, 800 Washington Street, Boston, MA, 02111, USA.
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Tischler
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000473:pathology*; D000328:Adult; D000818:Animals; D002648:Child; D004195:Disease Models, Animal; D005260:Female; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009368:Neoplasm Transplantation / Q000379:methods*; D010235:Paraganglioma / Q000473:pathology*; D010673:Pheochromocytoma / Q000473:pathology*; D014407:Tumor Cells, Cultured
keywords: NSG mouse; PDX; Paraganglioma; Pheochromocytoma; Xenograft