Post-transcriptional control of urokinase plasminogen activator expression in different cell lines derived from human thyroid tumors

The plasmin activating system has been shown to play a key role in growth and metastasis formation of many malignant tumors. However, informations regarding the expression of the different components of this system in thyroid tumors are limited. In the present study, we investigated the expression of the urokinase and tissue-type plasminogen activators (uPA and tPA), the uPA receptor (uPAR) and the two PAs inhibitors, PAI-1 and PAI-2 in normal (HTU5), follicular adenoma (HTU42), follicular carcinoma (FTC-133), papillary carcinoma (B-CPAP) and two anaplastic carcinoma (CAL-62 and 8305C) derived cell lines. To evaluate PAs activity, the different cell lines have been cultured for 24 h in absence of serum, after which surnatants have been analyzed by zymography, while total RNA was extracted from the different cell types to analyze the expression of the different genes by RT-PCR. The zymography results showed that the HTU5 and HTU42 cell lines secrete low levels of uPA but not tPA. The uPA activity was augmented in the surnatants of all carcinoma derived cell lines. In addition, the B-CPAP and the CAL62 cells also showed a low molecular weight uPA activity. However, RT-PCR analysis revealed the presence of uPA mRNA in all the cells analyzed without significant changes between the different lines, suggesting the occurrence of post-transcriptional mechanism(s) responsible for the higher uPA activity observed in all malignant thyroid tumors derived cell lines. The uPAR mRNA was also detected in all cell lines without significant modifications between them. Of the two PAIs, PAI-1 mRNA was equally expressed in all cell lines, while PAI-2 mRNA was absent in the CAL62 and reduced in the B-CPAP and FTC-133 cell lines. In conclusion, the data reported demonstrated a strong increase of uPA activity in all malignant thyroid tumor cell lines with respect to normal human thyrocytes and to benign follicular adenoma cells, and that post-transcriptional mechanism(s) are responsible for the increased enzyme activity. Moreover, our data also suggest that a reduction in PAI-2 expression may have a role in thyroid tumor progression