Role of tumor cell adhesion and migration in organ-specific metastasis formation

To form clinically evident metastases--the main cause of death in cancer patients--, tumor cells (TC) must complete a highly complex series of steps called the metastatic cascade, including local invasiveness, intravasation, circulation, adhesion and extravasation, survival, proliferation and angiogenesis. Since failure of any one of these steps results in metastatic failure, understanding the metastatic cascade may guide us to new therapeutic concepts. Here we review the role of specific TC adhesion and migration processes for organ-selective metastasis formation. TC adhesion in the microvasculature of host organs is a specific and highly regulated process mainly mediated by selectins for TC/endothelial cell binding and by integrins for TC/extracellular matrix interactions. Defined expression of the adhesion molecules and their corresponding ligands in the host organs and on the TC governs organ-selective non-random TC arrest. TC motility and subsequent chemotactically guided extravasation of adherent cells is the second rate-limiting step in organ-specific metastasis formation. Only if cells have completed adhesion and extravasation the growth of micrometastases and finally clinically evident metastases can occur.