International Protease Network

Department of Experimental Medicine
University of L'Aquila
Coppito 2, Via Vetoio, 67100 L?Aquila, Italy
Email: mackay@univaq.it
Tel: +39-0862-433542
Fax: +39-0862-433523
Homepage:

Research

We are interested in the transcriptional regulation of matrix metalloproteinases (MMP) and tissue inhibitor of metalloproteinases (TIMP), MMP activation mechanisms, substrate specificity and interaction with the plasmin system. We are also interested in identifying transcriptional and post transcriptional mechanisms that alter the equilibrium between MMPs and their specific tissue inhibitors.
Our main aim is to further understand the complexities involved in the regulation of MMP and TIMP expression during tumor progression, to identify MMPs that may promote or protect against tumor invasion, how MMPs interact with the plasmin system to regulate tumor invasion and angiogenesis and which mechanisms are employed by tumors to alter the MMP/TIMP equilibrium. Our studies are of particular relevance to human neuroblastoma and breast cancer.

Collaborations

Alberto Gulino, Univeristy of Rome, Italy
Arne Holmgren, Karolinska Instute, Sweden
Kathryn Tonnisen, Griffith University, Qld Australia
Unnur Thorgeirsson, NCI, NIH, Bethesda USA

Publications

Farina AR, Tacconelli A, Cappabianca L, DeSantis G, Gulino A, Mackay AR. Thioredoxin inhibits microvascular endothelial capillary tubule formation. Exp cell Res. 2003;291(2):474-483.

Cappabianca L, Farina AR, Tacconelli A, Mantovani R, Gulino A, Mackay AR. Reconstitution of TIMP-2 expression in SH-SY5Y neuroblastoma cells by 5-azacytidine is mediated transcriptionally by NF-Y through an inverted CCAAT site. Exp Cell Res. 2003;286(2):209-218.

Farina AR, Tacconelli A, Cappabianca L, Gulino A, Mackay AR. Inhibition of human MDA-MB-231 breast cancer cell invasion by matrix metalloproteinase 3 involves degradation of plasminogen. Eur J Biochem. 2002;269(18):4476-4483.

Farina AR, Masciulli MP, Tacconelli A, Cappabianca L, De Santis G, Gulino A, Mackay AR. All-trans-retinoic acid induces nuclear factor kappaB activation and matrix metalloproteinase-9 expression and enhances basement membrane invasivity of differentiation-resistant human SK-N-BE 9N neuroblastoma Cells. Cell Growth Differ. 2002;13(8):343-354.

Farina AR, Tacconelli A, Cappabianca L, Masciulli MP, Holmgren A, Beckett GJ, Gulino A, Mackay AR. Thioredoxin alters the matrix metalloproteinase/tissue inhibitors of metalloproteinase balance and stimulates human SK-N-SH neuroblastoma cell invasion. Eur J Biochem. 2001;268(2):405-413.