M. Griffin; "Extracellular Matrix...", 20.02.2006, 14:40, G032

Faculty of Engineering and Natural Sciences
FENS SEMINARS

Extracellular Matrix Changes Mediated by Tissue Transglutaminase can
Lead to Inhibition of Tumour Progression

Prof. Martin Griffin

Administration of active TG2 to two different in vitro angiogenesis assays resulted in the accumulation of a complex extracellular matrix (ECM) leading to the suppression of endothelial tube formation without causing cell death. Matrix accumulation was accompanied by a decreased rate of ECM turnover, with increased resistance to matrix metalloproteinase-1. Intratumor injection of TG2 into mice bearing CT26 colon carcinoma tumors demonstrated a reduction in tumor growth, and in some cases tumor regression. In TG2 knockout mice, tumor progression was increased and survival rate reduced compared to wild-type mice. In wild-type mice, an increased presence of TG2 was detectable in the host tissue around the tumor. Analysis of CT26 tumors injected with TG2 revealed fibrotic-like tissue containing increased collagen, TG2-mediated crosslink and reduced organized vasculature. TG2-mediated modulation of cell behavior via changes in the ECM may provide a new approach to solid tumor therapy.

Professor Griffin, Head of School for Life & Health Sciences at Aston University, Birmingham, UK. is a recognised international expert on transglutaminase enzymes. He has established national and international collaborative links with both academia and industry, the latter including companies such as Unilever Research, Smith and Nephew, ICI Pharmaceuticals (now Zeneca), ICI Central Toxicology Laboratories, BLC technology, Lumitech, Procyon ( Canada).  He has been a reviewer for a number of international journals including J Cell Biol, FASEB J. J Biol Chem and J Cell Science, acted as an invited panel member of the Portuguese Biological Sciences Review Board, an assessor of scientific quality for the National Research Foundation of S Africa and an invited reviewer of the Biological Sciences (teaching and Research) at the University of Riga, Latvia on behalf of the Latvian Department of Education. More recently he has been selected to sit on the Advisory Board of the Medical Research Council, UK.

Professor Griffin has published over 150 papers including 13 reviews and 10 book chapters and over 100 Conference Proceedings/Abstracts. He is also an inventor on 9 patent applications.  He has supervised over 30 PhD students and presently directs a research group of 5 post-doctoral research fellows, 5 research students and one research assistant. He has obtained over £5 million in awards and grants from such bodies as the BBSRC, EPSRC, Wellcome trust, Cancer Research Campaign, Diabetes UK, NKRF, Sir Halley Stewart Trust, Alan MacDonald Foundation (US), The Nobel Foundation (US), ICI Pharmaceuticals/ Toxicology, ICI Petrochemicals, Smith and Nephew, Unilever, the EU and BLC Leather Technology.

February 20, 2006, 14:40, G032