Establishment and characterization of a human parathyroid carcinoma derived cell line.

Parathyroid carcinoma is a rare neoplasia associated with PTH-dependent hypercalcaemia. It is infrequent in primary hyperparathyroidism (HPT) and very rarely associated with uremic HPT. A continuous cell line named Pt.Kich-1 from a parathyroid carcinoma diagnosed in a patient with secondary hyperparathyroidism (II° HPTH) was established and maintained in vitro for more than 60 passages. The cells were characterized for their immunophenotypic and endocrine characteristics as well as for their functional status after treatment by the extracellular [Ca(2+)]e, and the calcium homeostasis regulator 1α,25 (OH)2D3. The cytogenetic features were established by the R-banding. The Pt.Kich-1 cultures show an aspect of admixed epithelial/mesenchymal like cells with a doubling time between 96 and 112h. The cells are immunoreactive for cytokeratin (60%), EMA (26%), vimentin (46%), E-cadherin (32%), and synaptophysin (16%), while chromogranin A was not detected. Hypotetraploid karyotype containing large chromosomal markers and double minute chromosomes was identified in 30% of the metaphases. Treatment of Pt.Kich-1 cells with 1.0mM, 1.5mM, and 1.7mM of extracellular [Ca(2+)]e increased the DNA synthesis, while the calcium homeostasis regulator, the 1α,25 (OH)2D3, at 10(-9)-10(-7)M inhibited the cell growth. The levels of PTH measured in the medium of early cultures ranging between 547 and 610pg/μg of DNA declined during the passages to a level between 6 and 12pg/μg of DNA. No effect on the PTH release by the Pt.Kich-1 cells was observed after treatment with the all-trans (ATRA) and 9-cis retinoic acid differentiation inducers. The described in vitro cellular model can serve as a useful tool to study the pathogenesis of parathyroid carcinoma and to improve the knowledge of the molecular mechanisms involved in the control of gland sensitivity to [Ca(2+)]e leading to PTH synthesis and secretion.