Differential expression of the components of the plasminogen activating system in human thyroid papillary carcinomas

The plasminogen activating system (PAS) is implicated in multiple aspects of neoplastic progression and high tissue levels of PAS components correlate with a poor prognosis in different types of malignancies. In a previous work, we demonstrated an increased expression of uPA, uPAR and PAI-1 in human cell lines derived from different histotypes of malignant thyroid tumors, with respect to normal thyrocytes. In the present study we characterized, by means of western blot and real time RT-PCR, the expression of the plasminogen activators (uPA and tPA), the uPA receptor (uPAR) and the PAs inhibitors (PAI-1 and PAI-2) in 13 normal matched papillary thyroid carcinoma (PTC) tissues obtained following thyroidectomy. Quantitative RT-PCR analysis showed that uPA, uPAR and PAI-1 mRNAs were significantly increased by 4.42±0,95, 4.36±1.73 and 3.55±0.79 fold (p<0,01), respectively, in tumor tissues with respect to normal matched ones, while tPA and PAI-2 mRNAs were not significantly changed. The augmented expression of uPA and its receptor was confirmed at the protein level by western blot experiments performed on normal matched PTC tissues. Moreover, a significant correlation (p<0.01, r=0.709) between tumor size and uPA mRNA level, expressed as fold of increase versus normal matched tissue, was observed. We finally compared the fold of variation of the different PAS components mRNAs between PTC tissues from patients with (N1, n=4) or without (N0, n=8) lymph node metastases. Both uPA and uPAR mRNAs were significantly higher in metastatic PTC (p<0.05). In conclusion, we demonstrated that PTC overexpress uPA, uPAR and PAI-1, and that uPA overexpression correlates with PTC size. Furthermore, the expression of uPA and its cognate receptor was higher in metastatic PTC, suggesting their potential prognostic relevance in thyroid cancers, as already proved for other types of malignancies.