Differential expression of matrix metalloproteinases and plasminogen activators in normal and neoplastic human thyroid cell lines

Matrix metalloproteinases and the plasmin activating system have been shown to play a primary role in growth and metastasis formation of different types of tumors assuming, in some cases, a prognostic value. In the present study, we investigated the secretion of gelatinolytic (MMP-2 and MMP-9) and caseinolytic enzymes as well as of the plasminogen activators (PAs) from normal (HTU5) and from two anaplastic (CAL-62 and 8305C), one follicular (FTC-133) and one papillary (B-CPAP) human thyroid tumor cell lines. The expression of the different MMPs and PAs was also investigated by semiquantitative RT-PCR. To this end, the different cell lines have been cultured in appropriate serum-free culture media for 24 h, after which surnatants have been analyzed by zymography, while cells were employed to prepare total RNA. The results showed that the HTU5 cell line secretes MMP-2, but not MMP-9. A similar pattern was observed in the anaplastic cell line CAL-62. On the other hand, the anaplastic cell line 8305C, the FTC-133 and the B-CPAP presented an increased expression of MMP-2 and the induction of MMP-9 expression. HTU5, FTC-133 and CAL-62 cells did not show any caseinolytic activity, which was present in the 8305C and B-CPAP cell lines. All neoplastic cells displayed an higher secretion of the urokinase type PA with respect to that oberved in the surnatant of the HTU5 cell line. The levels of enzyme activities present in the surnatants of the different cell lines was in agreement with the observed levels of the corresponding mRNAs. In conclusion, the data reported demonstrated a differential expression of MMPs and PAs in the various thyroid tumor cell types analyzed with respect to normal human thyroid follicular cells. These findings may be useful in the understanding of the in vivo biological behaviour of different thyroid neoplasms.