Calcitonin receptors on neoplastic mononuclear cells cultured from a human giant-cell tumor of the sacrum.
Saturable, specific, high-affinity calcitonin receptors were demonstrated in cultured neoplastic mononuclear spindle cells from a giant-cell tumor of the sacrum of a 38-year-old woman. The receptor was analyzed by autoradiography and 125I-calcitonin binding assay. Binding reversibility of 125I-calcitonin to the cells was not complete and the structural specificity was indicated by the inability of unrelated hormones to compete with calcitonin. The 24,000 receptors/cell and dissociation constant (Kd) of 8.0 x 10(-10) M, calculated from linear Scatchard plots, suggested the existence of a single class of calcitonin binding sites in the neoplastic mononuclear cells. Flow-cytometric analysis in the primary culture showed that mononuclear cells consisted of mononuclear round cells of monocyte/macrophage lineage, which express more calcitonin receptors than neoplastic mononuclear spindle cells. Administration of calcitonin caused morphological and physiological alterations, resulting in involutional or irregular cytoplasmic shapes and inhibition of DNA synthesis in neoplastic mononuclear cells accompanied by the escape phenomenon. Cells preincubated with calcitonin showed a decrease in 125I-calcitonin binding activity, which could account for the escape phenomenon. The decrease in 125I-calcitonin binding was rapid, but the recovery was not observed for 24 h after elimination of calcitonin. This decrease may be caused by the disappearance of residual receptors or by a decrease in calcitonin affinity. The calcitonin-induced morphological changes and the inhibition of DNA synthesis of cells were revealed to be mediated by calcitonin receptors.
Maeda
A
A
Department of Orthopaedic Surgery, Toyama Medical and Pharmaceutical University, Faculty of Medicine, Japan.
Matsui
H
H
Kanamori
M
M
Yudoh
K
K
Tsuji
H
H
D000328:Adult; D001345:Autoradiography; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure*; D002116:Calcitonin / Q000378:metabolism / Q000494:pharmacology; D002462:Cell Membrane / Q000648:ultrastructure; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D005260:Female; D018212:Giant Cell Tumor of Bone / Q000382:microbiology / Q000473:pathology / Q000648:ultrastructure*; D006801:Humans; D007457:Iodine Radioisotopes; D007700:Kinetics; D018003:Receptors, Calcitonin / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D012447:Sacrum; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004273:DNA, Neoplasm; D007457:Iodine Radioisotopes; D018003:Receptors, Calcitonin; D002116:Calcitonin