THE ROLE OF CELL-ADHESION MOLECULES AND PROTEASES IN TUMOR INVASION AND METASTASIS

Over the past 10 years it has become apparent that invasion and metast asis are extremely complex processes; neoplastic cells must escape fro m the primary tumor, degrade the extracellular matrix, migrate to dist ant sites, arrest in the capillaries, and migrate through the basement membrane and underlying connective tissue to the metastatic site. The refore, tumor cells must exhibit considerable flexibility in their adh esive interactions, and this is reflected in a complex and dynamic exp ression pattern of cell adhesion molecules, proteases, protease inhibi tors, motility factors, and growth factors. Despite the recent explosi on of information regarding adhesion-related molecules, questions as t o their possible roles in normal tissue architecture and as to how alt erations in their expression or structure may be responsible for the p rogression from a single malignant cell to a lethal metastatic disease need further investigation. Moreover, efforts should be made to use t he obtained knowledge to contribute to improvements in the clinical ma nagement of cancer. In this review the different classes of cell adhes ion molecules and proteases are summarized, with special emphasis bein g placed on molecules that have been shown to correlate with invasion and metastasis. Furthermore, the role of E-cadherin in cell adhesion a nd invasive processes is discussed in more detail, since E-cadherin ma y be considered promising as a candidate among cell-adhesion-regulatin g molecules to be used as a biomarker for malignancy. We also elaborat e on the role of the catenins, which associate with and are important for the functioning of E-cadherin.