Over the past 10 years it has become apparent that invasion and metastasis are extremely complex processes; neoplastic cells must escape from the primary tumor, degrade the extracellular matrix, migrate to distant sites, arrest in the capillaries, and migrate through the basement membrane and underlying connective tissue to the metastatic site. Therefore, tumor cells must exhibit considerable flexibility in their adhesive interactions, and this is reflected in a complex and dynamic expression pattern of cell adhesion molecules, proteases, protease inhibitors, motility factors, and growth factors. Despite the recent explosion of information regarding adhesion-related molecules, questions as to their possible roles in normal tissue architecture and as to how alterations in their expression or structure may be responsible for the progression from a single malignant cell to a lethal metastatic disease need further investigation. Moreover, efforts should be made to use the obtained knowledge to contribute to improvements in the clinical management of cancer. In this review the different classes of cell adhesion molecules and proteases are summarized, with special emphasis being placed on molecules that have been shown to correlate with invasion and metastasis. Furthermore, the role of E-cadherin in cell adhesion and invasive processes is discussed in more detail, since E-cadherin may be considered promising as a candidate among cell-adhesion-regulating molecules to be used as a biomarker for malignancy. We also elaborate on the role of the catenins, which associate with and are important for the functioning of E-cadherin.
Cell adhesion molecules
To metastasize to different sites, cells that are usually in well-connected cell layers (such as epithelial cells) have to leave the tissue context, and at least a temporary weakening of the original intercellular interactions has to occur. This involves changes in homotypic cell-cell adhesion (adhesion molecules of one cell binding to identical molecules on a neighboring cell), heterotypic cell-cell adhesion (adhesion molecules on one cell binding to complementary partners on another cell), and interactions of