tailieunhanh - Báo cáo khoa học: Thrombin-mediated impairment of fibroblast growth factor-2 activity

Thrombin generation increases in several pathological conditions, including cancer, thromboembolism, diabetes and myeloproliferative syndromes. During tumor development, thrombin levels increase along with several other molecules, including cytokines and angiogenic factors. Under such conditions, it is reasonable to predict that thrombin may recognize new low-affinity substrates that usually are not recognized under low-expression levels conditions. | Thrombin-mediated impairment of fibroblast growth factor-2 activity Pierangela Totta1 z Raimondo De Cristofaro2 z Claudia Giampietri3 Maria S. Aguzzi1 Debora Faraone1 Maurizio C. Capogrossi1 and Antonio Facchiano1 1 Laboratorio di Patologia Vascolare IDI-IRCCS Istituto Dermopatico dell Immacolata-Istituto di Ricovero e Cura a Carattere Scientifico Rome Italy 2 Institute of InternalMedicine Haemostasis Research Center Catholic University Schoolof Medicine Rome Italy 3 Department of Histology and MedicalEmbriology University of Rome Sapienza Italy Keywords cell proliferation digestion fibroblast growth factor-2 maturation thrombin Correspondence A. Facchiano Laboratorio di Patologia Vascolare Istituto Dermopatico dell Immacolata IDI-IRCCS Via Monti di Creta 104 00167 Rome Italy Fax 39 06 6646 2430 Tel 39 06 6646 2431 E-mail These authors contributed equally to this work Received 6 October 2008 revised 19 March 2009 accepted 6 April2009 doi Thrombin generation increases in several pathological conditions including cancer thromboembolism diabetes and myeloproliferative syndromes. During tumor development thrombin levels increase along with several other molecules including cytokines and angiogenic factors. Under such conditions it is reasonable to predict that thrombin may recognize new low-affinity substrates that usually are not recognized under low-expression levels conditions. In the present study we hypothesized that fibroblast growth factor FGF -2 may be cleaved by thrombin and that such action may lead to an impairment of its biological activity. The evidence collected in the present study indicates that FGF-2-induced proliferation and chemo-taxis invasion of SK-MEL-110 human melanoma cells were significantly reduced when FGF-2 was pre-incubated with active thrombin. The inhibition of proliferation was not influenced by heparin. Phe-Pro-Arg-chlorom-ethyl ketone a specific inhibitor of the enzymatic activity of