Degradation of extracellular matrix by metastatic follicular thyroid carcinoma cell lines: Role of the plasmin activation system

The plasmin activation system plays a key role in extracellular matrix degr adation in many malignant tumors. Because no data are available on the invo lvement of the plasmin activation system in matrix degradation by thyroid c arcinoma, the present study was performed using follicular thyroid carcinom a cell lines obtained from a primary tumor (FTC-133) and metastases (FTC-23 6 and FTC-238) of one patient. Matrix degradation by these cell lines was s tudied assessing the release of radioactivity from S-35-methionine labeled extracellular matrix coated onto plastic. The involvement of constituents o f the plasmin activation system as well as matrix metalloproteinases (MMPs) , another class of proteolytic enzymes, which can be activated by plasmin, were assessed by semiquantitative reverse transcriptase-polymerase chain re action (RT-PCR) and zymography. In the matrix degradation experiment, S-35 release by FTC-133 was significa ntly higher than FTC-236 and FTC-238. S35 degradation could be inhibited by the plasmin inhibitor aprotinin and by anti-human urokinase-type plasminog en activator (uPA) antibody, indicating the involvement of the plasmin acti vation system. Matrix degradation could also be inhibited by the MMP inhibi tor marimastat, thus demonstrating the involvement of MMPs in matrix degrad ation by these cell lines. Zymographic assays revealed activity of uPA in a ll cell lines. However, in contrast with FTC-236 and FTC-238, no plasminoge n activator inhibitor (PAI) or PAI1 mRNA were found in FTC-133. Therefore, the differences in PAI activity as observed between the cell lines may orig inate from differences in PAI1 gene transcription. Differences in PAI1 expr ession did not affect the attachment of these cell lines to vitronectin. We conclude that the plasmin activation system is involved in extracellular m atrix degradation by these metastatic follicular thyroid carcinoma cell lin es. Differences in extracellular matrix degradation between the cell lines correspond with differences in PAI1 gene expression, indicating the signifi cance of PAI1 in extracellular matrix degradation by metastatic follicular thyroid carcinoma.