[Frontiers in Bioscience 16, 1861-1872, January 1, 2011]

The roles of ADAMTS metalloproteinases in tumorigenesis and metastasis

Laura Wagstaff1, Richard Kelwick2, Julie Decock2, Dylan R. Edwards2

1 Wellcome Trust/Cancer Research UK Gurdon Institute, The Henry Wellcome Building of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK, 2 Biomedical Research Centre, School of Biological Sciences, University of East Anglia, Norwich, Norfolk NR4 7JT, UK

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. The ADAMTS Family
4. The ADAMTSs in cancer biology
4.1. ADAMTS1
4.1.1. ADAMTS1 and inhibition of angiogenesis
4.1.2. Pro-tumorigenic/metastatic actions of ADAMTS1
4.2. ADAMTS8
4.3. ADAMTS9
4.4. ADAMTS12
4.5. ADAMTS13
4.6. ADAMTS15
4.7. ADAMTS18
5. Perspective
6. Acknowledgments
7. References

1. ABSTRACT

The human ADAMTS (a disintegrin and metalloproteinase with thrombospondin-like motifs) family of 19 secreted, multidomain proteolytic enzymes is involved in a wide range of biological processes including ECM assembly and degradation, hemostasis, organogenesis and the regulation of angiogenesis. Defects in certain family members give rise to inherited human genetic diseases, while aberrant expression of other ADAMTSs has been linked to the pathogenesis of arthritis and cancer. Several ADAMTSs act as tumor or metastasis suppressors whose functions are lost either by mutation or epigenetic silencing during tumor progression. This review looks in depth at the involvement of ADAMTSs as positive and negative mediators in cancer growth and spread.