Pleiotropic effects of thyroid stimulating hormone in a differentiated thyroid cancer cell line. Studies on proliferation, thyroglobulin secretion, adhesion, migration and invasion1

A. Zielke; S. Hoffmann; U. Plaul; Q.-Y. Duh; O. H. Clark; M. Rothmund

doi:10.1055/s-0029-1212127

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 1999; 107(6): 361-369
DOI: 10.1055/s-0029-1212127

Article

Pleiotropic effects of thyroid stimulating hormone in a differentiated thyroid cancer cell line. Studies on proliferation, thyroglobulin secretion, adhesion, migration and invasion¹

A. Zielke² , S. Hoffmann, U. Plaul, Q.-Y. Duh, O. H. Clark, M. Rothmund

Department of Surgery, Philipps-University of Marburg, Marburg, Germany (AZ, MR), Surgical Services, Department of Veterans Affairs Medical Center (Q-YD) and Mount Zion Medical Center (OHC) of the University of California at San Francisco, CA, USA

1 This work was supported in part by Grants of the Deutsche Forschungsgemeinschaft DFG (Zi386 1/1, Zi386 1/2)(AZ) and by the Medical Research Service of the VA and Mount Zion Health Systems.

Abstract

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Summary

Thyroid stimulating hormone (TSH) causes differentiation and epidermal growth factor (EGF) causes dedifferentiation of thyroid cells in vitro. In undifferentiated 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 Hiirthle cell origin (XTC), we 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 differentiated morphologic changes in XTC cells and stimulated secretion of human thyroglobulin in a dose dependent manner, whereas EGF did not. The effects of TSH on growth, adhesion, migration and invasion were dose dependent and biphasic, with an increase at low and a decrease at high concentrations of TSH. These effects were always more pronounced than those observed with EGF. Gelatino-lytic activity, consistent with metalloproteinase activity was revealed by zymography, but the pattern of secretion was not altered by neither TSH nor EGF. These results suggest, that TSH has pleiotropic effects on differentiated thyroid cancer cells in vitro that involve differentiated morphology and function but also affect features commonly associated with the malignant in vitro phenotype.

Key words

Oxyphilic (Hürthle) thyroid cancer - thyroid cancer cell line - growth factors - thyrotropin - in vitro invasion

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