ADAMs and Ectodomain Proteolytic Shedding in Leukocyte and Tumour Cell Migration

The ADAMs (a disintegrin and metalloproteinase) are a family of transmembrane proteins involved in ‘ectodomain shedding’ of adhesion molecules, chemokines, cytokines, cytokine receptors and growth factors. Metalloproteinase inhibitors, ADAM-deficient cells and cells expressing cleavage-resistant substrates have all been used to investigate the role of ADAMs in regulating cell adhesion and migration. In this chapter we will review the evidence for ADAM-dependent ectodomain shedding of cell adhesion molecules and chemokines in regulating leukocyte and tumour cell extravasation. Individual ADAMs are differentially regulated by alternative splicing, intracellular signalling pathways, cellular localization and availability of substrate. The regulation of ADAM10, 15 and 17 metalloproteinase activities during leukocyte extravasation and tumour cell metastasis will also be discussed.