Loss of dependence on IGF-1 for proliferation of human thyroid adenoma cells

The proliferative responses to IGF-1 (Somatomedin C) and TSH, as assessed by 3H-thymidine (3H-TdR) incorporation and autoradiographic labelling index (LI), of suspension and monolayer cultures of human thyroid follicular epithelium derived from both normal and adenoma tissue have been compared. In cultures of normal follicles, whilst neither TSH nor IGF-1 alone produced any effect, a combination of TSH (0.1 mU ml-1) together with IGF-1 (10 ng ml-1) induced a highly significant proliferative response as shown by a peak of 3HTdR incorporation and LI, 4-5 days after growth factor addition. The TSH concentration-effect curve was bell-shaped, a higher concentration of TSH (10 mU ml-1) resulting in a reduced response. In cultures derived from adenoma tissue, however, TSH alone at 0.1 mU ml-1 was sufficient to permit a highly significant proliferative response (equivalent to, or greater than the normal) in 4 out of 5 adenomas examined; again a higher concentration of TSH (10 mU ml-1) resulted in a diminished response. Addition of IGF-1 (10 ng ml-1) produced no significant change in the response to TSH (0.1 mU ml-1) in 3 of these 4 adenomas, and significantly inhibited the response in the fourth adenoma. It is concluded that escape from the requirement for an exogenous source of IGF-1 may be a key step in the development of human thyroid epithelial (follicular cell) neoplasia.