Dysregulation of cell-cell adhesion proteins, extracellular matrixproteins, cellular proteinases, apoptosis genes and other signaling peptides is an essential step of tumorigenesis and metastasis. Aims of these experiments were to study the roles of these factors on the tumorigenesis and metastasis of thyroid carcinoma. The expression of TSH receptor and E-Cadherin was lost during the dedifferentiation process and not detectable in undifferentiated thyroid carcinomas. CD97 could not be detected in normal tissue, however, was variably expressed in differentiated and strongly expressed in undifferentiated thyroid carcinomas. Expression of Matrixmetalloproteinases and their inhibitors could be detected in al tissues. Fas protein was down-regulated, Fas ligand war up-regulated in undifferentiated thyroid carcinomas. TSH, Forskolin, PMA and Insulin had no effect in vitro on the expression of CD97, MMP as well as TIMP, DR4, DR5 TRAIL, TNF-R1, Fas and Fas Ligand. EGF induced an increased expression of CD97, MMP-9, FasL and DcR-1 and decreased expression of E-Cadherin. Retinoic acid had an opposite effect. Alteration of TSH plasma concentration in physiological doses induced an ultrastructural change of the thyrocytes. Sensitivity or desensitivity of the hypothalamohypophysal-thyroidal axe depend on the application modus and doses of TSH used. High daily iodine intake induced an increase of TSH plasma concentration without changes of thyroid hormone concentration. Iodine deficiency led to a clearly decrease of T3 and T4 levels, and caused therefore an increase of TSH plasma concentration. A single irradiation with 4 Gy resulted in significant destruction of the follicular structure with a short term release of T3 most prominently in iodine deficiency but as well under normal and high iodine intake. However, only high or low iodine intake but not normal iodine supply stimulated the growth of thyroid carcinomas with high frequency (50 to 80% of animals after 110 weeks of observation vs. 0% in controls). |