ArticleProceedings of the National Academy of Sciences of the United States of America2014
Functional and genetic studies of isolated cells from parathyroid tumors reveal the complex pathogenesis of parathyroid neoplasia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 62 citations in OpenAlex.
- Molecular characterization of normal and physiologically suppressed human parathyroid glands at single-cell resolution.Journal of the Endocrine Society · 2026Article
- Immunohistochemical Expression of CaSR, VDR, and AMA in Parathyroid Tumors in Relation to Hypercalcemia Severity in Primary Hyperparathyroidism.Current issues in molecular biology · 2026Article
- Unraveling the mystery of parathyroid oxyphil cells in uremic SHPT: ongoing challenges and multi-omics advances.Journal of molecular cell biology · 2026Review
- The role of ESRRA and JUNB in oxyphil cells: insights from spatial transcriptomics and single-cell transcriptomics in uremic secondary hyperparathyroidism.Biology direct · 2026Article
- Importance of oxyphil cells for parathyroid hormone/calcium concentrations in primary hyperparathyroidism: a retrospective observational study.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026Observational
- Parathyroid glands exhibit reduced parenchymatic chief cells and increased extracellular collagen as a response to a long-term low-phosphorus diet in pigs.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- Lesion size and cystic morphology are key determinants of parathyroid hormone washout in primary hyperparathyroidism.Frontiers in endocrinology · 2025Article
- Single-cell analysis reveals transcriptional dynamics in healthy primary parathyroid tissue.Genome research · 2024Article
- KMT2A and chronic inflammation as potential drivers of sporadic parathyroid adenoma.Clinical and translational medicine · 2024Article
- Molecular and Clinical Spectrum of Primary Hyperparathyroidism.Endocrine reviews · 2023Article
- Establishment and characterization of long-term human primary parathyroid tumor subclones derived from Indian PHPT.3 Biotech · 2023Article
- Common Key Genes in Differentiating Parathyroid Adenoma From Thyroid Adenoma.Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme · 2023Article
- Digital spatial profiling of human parathyroid tumors reveals cellular and molecular alterations linked to vitamin D deficiency.PNAS nexus · 2023Article
- Single-cell RNA sequencing reveals the role of cell heterogeneity in the sex difference in primary hyperparathyroidism.Frontiers in endocrinology · 2023Article
- MicroRNA Profile Alterations in Parathyroid Carcinoma: Latest Updates and Perspectives.Cancers · 2022Review
- Ex Vivo Intact Tissue Analysis Reveals Alternative Calcium-sensing Behaviors in Parathyroid Adenomas.The Journal of clinical endocrinology and metabolism · 2021Article
- mRNA Profiles of Porcine Parathyroid Glands Following Variable Phosphorus Supplies throughout Fetal and Postnatal Life.Biomedicines · 2021Article
- Intratumor heterogeneity in human parathyroid tumors.Histology and histopathology · 2020Review
- Immunocyte density in parathyroid carcinoma is correlated with disease relapse.Journal of endocrinological investigation · 2020Article
- Dysregulated mitogen-activated protein kinase pathway mediated cell cycle disruption in sporadic parathyroid tumors.Journal of endocrinological investigation · 2020Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Parathyroid adenomas (PAs) causing primary hyperparathyroidism (PHPT) are histologically heterogeneous yet have been historically viewed as largely monotypic entities arising from clonal expansion of a single transformed progenitor. Using flow cytometric analysis of resected adenomatous parathyroid glands, we have isolated and characterized chief cells, oxyphil cells, and tumor-infiltrating lymphocytes. The parathyroid chief and oxyphil cells produce parathyroid hormone (PTH), express the calcium-sensing receptor (CASR), and mobilize intracellular calcium in response to CASR activation. Parathyroid tumor infiltrating lymphocytes are T cells by immunophenotyping. Under normocalcemic conditions, oxyphil cells produce ∼50% more PTH than do chief cells, yet display significantly greater PTH suppression and calcium flux response to elevated calcium. In contrast, CASR expression and localization are equivalent in the respective parathyroid cell populations. Analysis of tumor clonality using X-linked inactivation assays in a patient-matched series of intact tumors, preparatively isolated oxyphil and chief cells, and laser-captured microdissected PA specimens demonstrate polyclonality in 5 of 14 cases. These data demonstrate the presence of functionally distinct oxyphil and chief cells within parathyroid primary adenomas and provide evidence that primary PA can arise by both clonal and polyclonal mechanisms. The clonal differences, biochemical activity, and relative abundance of these parathyroid adenoma subpopulations likely reflect distinct mechanisms of disease in PHPT.
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