Pleiotropic effects of thyroid stimulating hormone in a differentiated thyroid cancer cell line. Studies on proliferation, thyroglobulin secretion, adhesion, migration and invasion

Thyroid stimulating hormone (TSH) causes differentiation and epidermal grow th factor (EGF) causes dedifferentiation of thyroid cells in vitro. In undi fferentiated thyroid cancer cell lines, TSH stimulates tumor cell migration and invasion, a dedifferentiated function, presumably due to an escape of tumor cells from the control of differentiating growth factors. In a highly differentiated thyroid carcinoma cell line of Hurthle cell origin (XTC), w e tested the hypothesis that TSH would stimulate thyroglobulin secretion (a differentiated function) more than EGF, and EGF would stimulate invasion ( a de-differentiated function) more than TSH. Proliferation, adhesion, cell migration and invasion were measured by the MTT assay, human thyroglobulin by RIA and protease activity by substrate-gel zymography. TSH induced diffe rentiated morphologic changes in XTC cells and stimulated secretion of huma n thyroglobulin in a dose dependent manner, whereas EGF did not. The effect s of TSH on growth, adhesion, migration and invasion were dose dependent an d biphasic, with an increase at low and a decrease at high concentrations o f TSH. These effects were always more pronounced than those observed with E GF Gelatinolytic activity, consistent with metalloproteinase activity was r evealed by zymography, but the pattern of secretion was not altered by neit her TSH nor EGF These results suggest, that TSH has pleiotropic effects on differentiated thyroid cancer cells in vitro that involve differentiated mo rphology and function but also affect features commonly associated with the malignant in vitro phenotype.