Immunocytochemical characterization of two thyroid medullary carcinoma cell lines in vitro

Abstract

The immunocytochemical characterization of cell lines originating from thyroid medullary carcinoma, i.e. human TT cells and rat rMTC 6-23 cells, was undertaken. The immunocytochemical studies were supplemented by ultrastructural studies, including ultrastructural immunocytochemistry, and by radioimmunological estimation of calcitonin secretion to the medium. In rMTC 6-23 cells (subcultures 24 to 30), no hormone presence was demonstrated immunocytochemically, which corresponded to the absence of secretory granules at the ultrastructural level. Of various proteins sought, only neuron-specific enolase could be demonstrated. Nevertheless, the cells secreted calcitonin into the medium. TT cells (passages 145 to 160) produced secretory granules. The granules contained calcitonin, calcitonin gene-related peptide, somatostatin, neurotensin, met-enkephalin, leu-enkephalin, gastrin releasing peptide, parathyroid hormone-related protein, functional proteins of the chromogranin group and synaptophysin. Other functional proteins found in the cytosol of TT cells included non-specific enolase, calbindin and tyrosine hydroxylase. Receptor for calcitriol was localized in the cell nucleus. Marker proteins were localized in the cytosol (carcinoembryonic antigen) and in the cell skeleton (alpha-tubulin, cytokeratin). Following changes in ionized calcium levels in the medium, changes in calcitonin secretion and in immunocytochemical detectability of some hormones and functional proteins were observed. TT cells demonstrated the expression of numerous hormones and functional proteins associated with calcitonin secretion. Further, the cells in their ultrastructure, immunocytochemical and secretory characteristics, resemble more closely normal parafollicular cells of the thyroid and, in our opinion, represent a more appropriate model for functional studies.

Expression of hypothalamic regulatory peptides in thyroid C cells of different mammals

“…Scale bar: 20 lm, in low magnifications; 10 lm, in inserts. rat CA-77 cells (Aron and Roos, 1986), while Zabel et al described its presence in human TT cells but not in rat MTC 6-23 (Zabel et al, 1995). All previous results have been confirmed by us in the present paper.…”

Src Homology-2-Containing Protein Tyrosine Phosphatase-1 Restrains Cell Proliferation in Human Medullary Thyroid Carcinoma

“…TT cells express and secrete calcitonin, carcinoembryonic antigen, chromogranin A, and many other peptides (18). TT cells harbor a MEN-2A-type mutation (19), with a cysteine-to-tryptophan substitution at the level of the RET codon 634 (13), and a glycine-to-serine at codon 691 in exon 11, reported to be a RET polymorphism (20).…”

Cyclooxygenase-2 Inhibitors Reverse Chemoresistance Phenotype in Medullary Thyroid Carcinoma by a Permeability Glycoprotein-Mediated Mechanism

“…TT cells express and secrete calcitonin, carcinoembryonic antigen, chromogranin A, and many other peptides (7).…”