Immunochemical heterogeneity of calcitonin in tumor, tumor venous effluent, and peripheral blood of patients with medullary thyroid carcinoma.

Abstract

Abstract CT circulates in the plasma of patients with MTC, and possibly of normal people, as several (three to five) immunochemical species of differing apparent molecular size. In order to investigate the origins of this immunochemical heterogeneity, we chromatographed (on columns of Bio-Gel P-150) material from two patients with MTC: tumor extracts, tumor venous effluent plasma (one case), and peripheral plasma from the basal state, after pentagastrin injection, and after long (4 hr) and short (10 min) infusions of calcium. The CT immunoreactivity in column effluent fractions was measured using antiserum G-1701, directed predominantly toward the amino acid sequence region 17–28 of hCT. Tumor extracts contained at least three major immunochemical species: one eluting near the V 0 , one eluting with a K d near that of radioiodinated hCT dimer, and one co-eluting with CT 1–32 monomer. CT monomer comprised only 20% and 33% of total immunoreactivity in tumor extracts. The elution profile of CT in a tumor venous effluent sample was similar to that in its corresponding tumor extract, CT monomer being 31% of the total. Under basal conditions, peripheral plasma again yielded three major peaks of immunoreactivity; material co-eluting with CT monomer comprised only 37% and 36% of total immunoreactivity. In plasma from the fourth hour of calcium infusion, the quantities of all immunochemical forms were increased proportionately. However, after rapid intravenous injection of pentagastrin, CT monomer concentrations rose disproportionately, comprising 53% of the total immunoreactivity in each case. After a short calcium infusion (10 min) the elution profile was similar to that after pentagastrin: CT monomer predominated (52%). These results suggest that the immunochemical heterogeneity of circulating CT may arise within the C-cells but that the relative proportions of immunochemical forms in peripheral blood may vary under different conditions. Acute stimulation of CT secretion, whether by calcium or pentagastrin, increases the ratio of CT monomer to other forms.