Abstract
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.
Highlights
Investigation of the possible cellular mechanisms which may be implicated in the process of neoplastic transformation, requires an in vitro model
We have previously demonstrated that a proliferative response to TSH could be obtained in cultures of normal human thyroid follicular cells, but required the presence of a combination of two permissive factors, namely a supraphysiological level of insulin coupled with a low concentration of serum
Our present data demonstrate that the permissive effect of insulin and serum in suspension cultures of normal human thyroid follicles can be substituted for by a physiological concentration of a single permissive factor, namely IGF-1, a combination of IGF-l and TSH producing a highly significant peak of 3H-TdR incorporation occurring on day 4-5 of the culture period
Summary
Investigation of the possible cellular mechanisms which may be implicated in the process of neoplastic transformation, requires an in vitro model. It was postulated that this combination of insulin and FCS resulted in activation of the cellular IGF-1 (Somatomedin-C) receptor which is known to have an important role in the regulation of proliferation in diverse cell types (Van Wyk & Underwood, 1978). In this communication, we demonstrate that insulin and FCS can be substituted by a physiological concentration of IGF-1, a combination of IGF-I with TSH
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