Expression of the components of the plasminogen activating system in benign and malignant thyroid tumor lesions

Plasminogen activating system (PAS) is implicated in multiple aspects of neoplastic progression, and clinical evidences demonstrated that high tissue levels of PAS components correlate with a poor prognosis in different types of malignancy. In previous experiments we demonstrated an increased expression of the urokinase plasminogen activator (uPA), of the uPA receptor (uPAR) and of the PA inhibitor 1 (PAI-1,) in human cell lines derived from malignant thyroid tumor, with respect to normal human thyrocytes. In the present study we characterized, by means of semiquantitative RT-PCR, the expression of uPA, uPAR, PAI-1 and PAI-2 in three benign follicular adenomas (FA) and three papillary thyroid carcinomas (PTC), and compared to that found in normal tissues obtained from the same patients following thyroidectomy. Total RNA was extracted from tissue samples by the acid guanidinium thiocyanate-phenol-chloroform method and analyzed in RT-PCR using specific primers. To determine the specificities of amplified cDNAs, they were recovered from the gel, purified and subjected to sequencing reactions. The obtained results showed that uPA mRNA was undetectable in all normal thyroid tissues but induced in one FA and two out of three PTC. Low levels of uPAR mRNA were observed in all normal thyroid tissues and increased in two FA and in all PTC. Both PAI-1 and PAI-2 mRNAs were not or barely detectable in normal tissues, to be up-regulated in one case of FA. PAI-1 mRNA was found to be augmented in all PTC, while PAI-2 mRNA was reduced in 1 and induced in 2 cases of PTC. In conclusions, the data here reported confirm our previous observation on normal and malignant thyroid tumor derived cell lines, demonstrating that the expression of the different components of PAS is altered during thyroid cancer progression. This will warrant further studies in order to determine the possible prognostic value of these proteins in thyroid carcinomas and whether they may represent potential molecular targets for therapeutic treatment of these malignancies.