Mechanisms of metastasis.

The metastatic spread of solid tumours is responsible directly or indirectly for most cancer-related deaths. Our understanding of the molecular genetic and biological events that contribute to tumor cell dissemination has increased considerably over the last decade. It is clear that close anatomic and temporal co-operation between cellular adhesion molecules, extracellular matrix (ECM)-degrading proteases and peptides inducing tumour vascularisation are essential components of the metastatic behaviour of cancer cells. Although this enhanced understanding may have little immediate impact on patient survival (about 50% of patients have established metastatic disease at first presentation), it has led to the development of novel anti-metastatic therapies targeting distinct molecules and steps in the metastatic cascade. Here we review the role of matrix-degrading enzymes, changes in cellular adhesive capacity and tumour angiogenesis during cancer spread, highlighting areas that are of emerging importance in the clinic.