PARACRINE EFFECT OF HUMAN CHORIONIC-GONADOTROPIN ECTOPICALLY PRODUCEDFROM PAPILLARY THYROID-CANCER CELLS ON GROWTH AND FUNCTION OF FRTL-5 RAT-THYROID CELLS

It is well known that human chorionic gonadotropin (hCG) is sometimes secreted from nontrophoblastic neoplasms. To elucidate the role of ect opic hCG, we investigated the effect of hCG produced from a papillary thyroid cancer cell line (B-CPAP cells) on stimulation and growth prom otion of FRTL-5 rat thyroid cells. Ectopic hCG contained in the cultur e medium of B-CPAP cells was purified using gel filtration and bioassa yed for thyrotropic activity in FRTL-5 cells. Addition of ectopic hCG (up to 5.2 x 10(4) IU/L) increased cyclic adenosine monophosphate (cAM P) accumulation and H-3-thymidine incorporation in FRTL-5 cells dose d ependently. These effects were almost as potent as the stimulation ind uced by standard hCG CR-127. After the absorption of the ectopic hCG b y anti-hCG-beta monoclonal antibody, the cAMP accumulation was signifi cantly decreased. Analysis of ectopic hCG isoforms with different isoe lectric points indicated the predominance of the acidic hCG isoform wi th isoelectric point (pI) 3.8-3.2 that is the major isoform of standar d hCG. Basic isoforms (pI 5.7-5.3) with higher thyrotropic potency wer e also detected. These results indicate that the ectopic hCG secreted from papillary thyroid cancer cells possess intrinsic thyroid-stimulat ing and growth-promoting activity. The ectopic hCG may act as an autoc rine-paracrine factor in nontrophoblastic neoplasms.