THE METASTATIC CASCADE The metastatic cascade is illustrated schematically in Figure 1. Having disengaged from its primary site the metastatic tumour cell must invade the surrounding stroma, enter the vasculature or lymphatic system, survive and arrest at a distant site. From here it extravasates into the tissue and, after elaboration of a blood supply, grows and develops into a secondary mass. The parallels between many of these steps and those involved in the migratory behaviour of leucocytes during inflammation or the initiation of new tissue growth and angiogenesis during wound healing have provided the identity of many of the molecules thought to be involved in tumour dissemination. Key processes involved include changes in cellular adhesion, the production of proteolytic enzymes capable of degrading the stroma and the secretion of a variety of cytokines which attract and activate stromal cells and endothelial cells during invasion and angiogenesis.

CELL ADHESION MOLECULES (CAMs) The initial escape of a tumour cell from its primary site requires the loss of cell±cell attachment which, in epithelial tumours, is mediated largely by the members of the cadherin family and in particular by E-cadherin. Alterations also occur in the nature of adhesion events between the released tumour cells and the extracellular matrix which allow the motile neoplastic cells to migrate over underlying substrates. Integrins are of prime importance in these cell-substrate interactions.