Endocrine Abstracts

We have recently shown that Tie-2, the receptor for the angiopoietins, is expressed on thyroid follicular cells. This angiogenic receptor was previously thought to be restricted to the endothelium where it influences the maturation of blood vessels. The role of Tie-2 in the growth, function and follicular architecture of thyroid cells is unknown. We have used primary cultures of human thyroid cells and the rat thyroid cell line, FRTL5 to examine the role of this axis. We have constructed a truncated form of Tie-2 expressed in replication-defective adenovirus (RAd-sTie-2). We found that truncated Tie-2 was secreted (Western blotting) and could complex secreted endogenous angiopoietins, thus negating Tie-2 signalling. Infection of FRTL5 thyroid cells with RAd-sTie-2 resulted in a loss of cell adherence to the culture dish. This was not due to adenoviral infection per se as control cells infected with RAd-Green fluorescent protein remained healthy and attached. Cells were not apoptotic and were able to reattach to the culture dish when sTie-2 was removed. This effect was even more marked when FGF-2, a potent mitogen for these cells, was included. In human thyroid cells, infection with RAd-sTie-2 reduced their ability to form 3D follicular structures and inhibited ¹²⁵I uptake. As for FRTL5 cells, adhesion and growth were inhibited. Attachment to the substratum is thus mediated either through Tie itself or through the angiopoietins. We conclude that the Tie-2 receptor has a functional role in thyroid follicular cells.