Transplantable rat thyroid cancer cell line FRTC transformed with muramyl dipeptide

Abstract

A rat thyroid cancer cell line, FRTC, was established from the normal rat thyroid cell line, FRTL-5. FRTL-5 cells were cultured in vitro with N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) for 4 days and were transplanted intraperitoneally into Fisher rats. Disseminated tumour formation in the peritoneum was found in ten out of ten rats in which MDP-treated FRTL-5 cells were transplanted. Colloid-like structures stained with anti-thyroglobulin (Tg) antibodies were observed in the tumours. On the other hand, no tumour was found in any of the rats in which untreated FRTL-5 cells were transplanted. No morphological changes were observed in FRTL-5 cells after long-term in vitro culture in the presence of MDP. MDP had no effect on thymidine incorporation, the production of cAMP or the expression of c-myc in FRTL-5 cells in vitro. Cells from the tumour (FRTC) secreted Tg in vitro and expressed Tg, thyroid peroxidase (TPO) and thyrotropin (TSH) receptor mRNA. The expression of TSH receptor mRNA increased in FRTC cells after TSH stimulation. FRTC cells produced cAMP in response to TSH stimulation in a dose-dependent manner. However, the growth of FRTC cells was TSH independent. Expression of c-myc and c-fos was observed in FRTC cells in vivo as well as in vitro. FRTC cells formed tumours in Fisher rats when transplanted subcutaneously. FRTC cells have several characteristics of differentiated thyroid cancer cells and may provide a good model for the study of human differentiated thyroid cancers.