ECE2023 Poster Presentations Endocrine-related Cancer (62 abstracts)
Cellular models of parathyroid carcinoma: preliminary results
Gaia Palmini 1 , Francesca Marini 2 , Francesca Giusti 1,3 , Simone Donati 1 , Cinzia Aurilia 1 , Irene Falsetti 1 , Roberto Zonefrati 2 , Giuliano Perigli 4 , Roberto Santoro 4 , Gabriella Nesi 5 & Maria Luisa Brandi 2,3
1University of Florence, Experimental and Clinical Biomedical Sciences, Florence, Italy; 2Fondazione Italiana Ricerca sulle Malattie dell’Osso (FIRMO Onlus), Florence, Italy; 3Villa Donatello, Bone Clinic, Sesto Fiorentino, Italy; 4University of Florence, Experimental and Clinical Medicine, Florence, Italy; 4University of Florence, Experimental and Clinical Medicine, Florence, Italy
Parathyroid carcinoma (PC) is an extremely rare endocrine malignancy of the parathyroid glands, representing less than 1% of all parathyroid neoplasms. PC is characterized by an excessive secretion of parathyroid hormone (PTH) and severe hypercalcemia. In contrast to parathyroid adenoma, the prognosis for patients with PC is poor, with an overall survival rate of 78-85% and 49-70% respectively at 5 and 10 years after diagnosis, due to the commonly unmanageable hypercalcaemia, which is the cause of death in most cases. There are currently no decisive therapies available for PC. The main treatment for PC remains surgical removal of the tumour gland(s), but persistent, or recurrent post-surgical disease is reported in about 50% of patients. A better understanding of the biology and pathophysiology of PC is necessary to advance is not only too better in distinguishing PC from benign counterpart, but also to develop novel targeted and effective therapies. The principal aim of this research is to establish an in vitro model of human primary cell line of PC, to evaluate the presence of cancer stem cells (CSCs), and to isolate and characterize them. We established a primary cell culture of from a primary sporadic PC lesion. Hence, the PC phenotype was evaluated by immunofluorescence staining for PTH, ki67, Desmin, CaSR protein, parafibromin, and by evaluation of PTH release. We evaluated the ability of PC cells to form spherical colonies under non adherent conditions to identify and isolate PC cancer stem cells (PC-CSCs). Cells isolated through this particular assay were then characterized by: 1) immunofluorescence staining for mesenchymal stem cell (MSC) markers, 2) immunofluorescence staining for PTH, ki67, Desmin, CaSR protein, parafibromin, 3) quantitative RT-PCR analyses of gene expression of the embryonic stem cell (ESC) marker genes (i.e., KLF4, POU5F1, Nanog and SOX2) and of the PTH gene, and 4) ELISA dosage of the PTH extracellular release. The obtained preliminary results showed that we established a primary human PC cell line and that we isolated, for the first time, a PC-CSCs line, presenting the phenotypic characteristics typical of CSCs and the classical features of parathyroid principal cells, such as CaSR expression and PTH expression and release. Further investigations are ongoing to completely characterized both the primary PC cell line and the PC-CSCs. In conclusion, these established cell models could pave the way to better understand the biology of PC cells, and the basis of parathyroid malignant carcinogenesis and aggressiveness of PCs.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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