The human chondrosarcoma cell line (HCS-2/8) established by our group expresses cartilage phenotypes such as production of cartilage-type proteoglycans and collagen type II, but its tumorigenicity is low. To develop an in vitro experimental system for studies of human chondrosarcomas, a new immortal cell line of human chondrosarcoma, named HCS-2/A, was established from the same tumor. HCS-2/A cells proliferated with a doubling time of 3 1/2 days in a medium containing 20% fetal bovine serum (FBS). This growth rate was comparable to that of HCS-2/8 cells. However, HCS-2/A cells proliferated more rapidly than HCS-2/8 cells in the presence of 2-10% FBS. Like HCS-2/8 cells, HCS-2/A cells had a polygonal shape in sparse cultures and became spherical as they reached confluence, after which they formed nodules composed of multilayered cells and a large quantity of extracellular matrix showing strong metachromasia. The nodules formed by HCS-2/A cells were thicker and also larger in diameter than those formed by HCS-2/8 cells. Electron microscopically, the cells in the nodules resembled chondrocytes in vivo, but each cell had an irregular-shaped nucleus which is a characteristics of tumor cells. The cells actively synthesized "cartilage-specific" large proteoglycans and their level of proteoglycan synthesis was comparable to that of HCS-2/8 cells. Insulin, which stimulates proteoglycan and DNA syntheses in cultured chondrocytes, markedly increased proteoglycan synthesis in HCS-2/A cells. On the other hand, the hormone only slightly increased proteoglycan synthesis in HCS-2/8 cells. Insulin also stimulated DNA synthesis in cultured HCS-2/A cells, but not in HCS-2/8 cells. Immunostaining revealed that HCS-2/A cells produced type-II collagen but not type-I collagen. However, the level of collagen synthesis of HCS-2/A cells was lower than that of HCS-2/8 cells. Inoculation of HCS-2/A cells into athymic mice resulted in the formation of chondrosarcomas that grew faster than those arising from HCS-2/8 cells.

No abstract

We studied the effect of lithium on the release of T3, T4, and cAMP from perifused mouse thyroids and on cAMP content in thyroid pieces. Lithium significantly inhibited T3 and T4 release from TSH-stimulated mouse thyroids. This inhibitory effect on thyroid hormone release was dependent on the concentration of lithium. Under continuous stimulation with TSH and 3-isobutyl-1-methylxanthine, both cAMP release and cAMP content were significantly decreased by lithium. In addition, we studied the effect of lithium on (Bu)2cAMP-stimulated thyroid hormone release. T3 and T4 release was stimulated by (Bu)2cAMP in a similar way to TSH. Lithium significantly inhibited (Bu)2 cAMP-stimulated T3 and T4 release from perifused mouse thyroids. These results suggest that lithium inhibits the action of TSH in the thyroid gland by both suppression of cAMP production and inhibition at a step beyond cAMP generation.

No abstract