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Originally published online as doi:10.2353/ajpath.2009.080979 on July 30, 2009

Published online before print July 30, 2009
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(American Journal of Pathology. 2009;175:1200-1207.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.080979

Expression of Parathyroid-Specific Genes in Vascular Endothelial Progenitors of Normal and Tumoral Parathyroid Glands

Sabrina Corbetta*, Marzia Belicchi{dagger}, Federica Pisati{dagger}, Mirella Meregalli{dagger}, Cristina Eller-Vainicher{ddagger}, Leonardo Vicentini§, Paolo Beck-Peccoz{ddagger}, Anna Spada{ddagger} and Yvan Torrente{dagger}

From the Endocrinology and Diabetology Unit,* Department of Medical-Surgical Sciences, Università di Milano, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico S. Donato, S. Donato M. se, Italy; the Stem Cell Laboratory,{dagger} Department of Neurological Sciences, Università di Milano, IRCCS Fondazione Ospedale Maggiore, Regina Elena e Mangiagalli, Centro Dino Ferrari, Italy; the Endocrine Unit,{ddagger} Department of Medical Sciences, Università di Milano, IRCCS Fondazione Ospedale Maggiore, Regina Elena e Mangiagalli; and Endocrine Surgery,§ IRCCS Fondazione Ospedale Maggiore, Regina Elena e Mangiagalli, Milan, Italy

Parathyroid tissue is able to spontaneously induce angiogenesis, proliferate, and secrete parathyroid hormone when autotransplanted in patients undergoing total parathyroidectomy. Angiogenesis is also involved in parathyroid tumorigenesis. Here we investigated the anatomical and molecular relationship between endothelial and parathyroid cells within human parathyroid glands. Immunohistochemistry for CD34 antigen identified two subpopulations in normal and tumoral parathyroid glands: one constituted by cells lining small vessels that displayed endothelial antigens (factor VIII, isolectin, laminin, CD146) and the other constituted of single cells scattered throughout the parenchyma that did not express endothelial markers. These parathyroid-derived CD34+ cells were negative for the hematopoietic and mesenchymal markers CD45, Thy-1/CD90, CD105, and CD117/c-kit; however, a subset of CD34+ cells co-expressed the parathyroid specific genes glial cell missing B, parathyroid hormone, and calcium sensing receptor. When cultured, these cells released significant amount of parathyroid hormone. Parathyroid-derived CD34+ cells, but not CD34– cells, proliferated slowly and differentiated into mature endothelial cells. CD34+ cells from parathyroid tumors differed from those derived from normal parathyroid glands as: 1) they were more abundant and mainly scattered throughout the parenchyma; 2) they rarely co-expressed CD146; and 3) a fraction co-expressed nestin. In conclusion, we identified cells expressing endothelial and parathyroid markers in human adult parathyroid glands. These parathyroid/endothelial cells were more abundant and less committed in parathyroid tumors compared with normal glands, showing features of endothelial progenitors, which suggests that they might be involved in parathyroid tumorigenesis.






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