In Vitro and In Vivo Effects of the Urokinase Plasminogen Activator Inhibitor WX-340 on Anaplastic Thyroid Cancer Cell Lines |
| |
| Authors: | Enke Baldini,Dario Presutti,Pasqualino Favoriti,Simonetta Santini,Giuliana Papoff,Chiara Tuccilli,Raffaella Carletti,Cira Di Gioia,Eleonora Lori,Iulia Catalina Ferent,Federica Gagliardi,Antonio Catania,Daniele Pironi,Domenico Tripodi,Vito D’ Andrea,Salvatore Sorrenti,Giovina Ruberti,Salvatore Ulisse |
| |
| Affiliation: | 1.Department of Surgical Sciences, “Sapienza” University of Rome, 00161 Rome, Italy; (E.B.); (P.F.); (C.T.); (E.L.); (I.C.F.); (F.G.); (A.C.); (D.P.); (D.T.); (V.D.); (S.S.);2.Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), Monterotondo, 00015 Rome, Italy; (D.P.); (S.S.); (G.P.); (G.R.);3.Department of Radiological, Oncological and Pathological Sciences, “Sapienza” University of Rome, 00161 Rome, Italy; (R.C.); (C.D.G.) |
| |
| Abstract: | Increased expression of the urokinase-type plasminogen activator (uPA) system is associated with tumor invasion, neo-angiogenesis, and metastatic spread, and has been shown to positively correlate with a poor prognosis in several cancer types, including thyroid carcinomas. In recent years, several uPA inhibitors were found to have anticancer effects in preclinical studies and in some phase II clinical trials, which prompted us to evaluate uPA as a potential therapeutic target for the treatment of patients affected by the most aggressive form of thyroid cancer, the anaplastic thyroid carcinoma (ATC). In this study, we evaluated the in vitro and in vivo effects of WX-340, a highly specific and selective uPA inhibitor, on two ATC-derived cell lines, CAL-62 and BHT-101. The results obtained indicated that WX-340 was able to reduce cell adhesion and invasiveness in a dose-dependent manner in both cell lines. In addition, WX-340 increased uPA receptor (uPAR) protein levels without affecting its plasma membrane concentration. However, this compound was unable to significantly reduce ATC growth in a xenograft model, indicating that uPA inhibition alone may not have the expected therapeutic effects. |
| |
| Keywords: | anaplastic thyroid cancer urokinase plasminogen activator WX-340 xenograft proliferation cell adhesion cell migration BHT-101 CAL-62 |
|
|
