Tumor cell adhesion under hydrodynamic conditions of fluid flow

Current evidence indicates that tumor cell adhesion to the microvasculature in host organs during formation of distant metastases is a complex process involving various types of cell adhesion molecules. Recent results have sh own that stabilization of tumor cell adhesion to the microvascular vessel w all is a very important step for successful tumor cell migration and coloni zation of host organs. We are beginning to understand the influences of flu id flow and local shear forces on these adhesive interactions and cellular responses within the circulation. Mechanosensory molecules or molecular com plexes can transform shear forces acting on circulating tumor cells into in tracellular signals and modulate cell signaling pathways, gene expression a nd other cellular functions. Flowing tumor cells can interact with microvas cular endothelial cells mediated mainly by selectins, but the strength of t hese bonds is relatively low and not sufficient for stable cell adhesions. Integrin-mediated tumor cell adhesion and changes in the binding affinity o f these adhesion molecules appear to be required for stabilized tumor cell adhesion and subsequent cell migration into the host organ. Failure of the conformational affinity switch in integrins results in breaking of these bo nds and recirculation or mechanical damage of the tumor cells. Various cell signaling molecules, such as focal adhesion kinase, pp60src or paxillin, a nd cytoskeletal components, such as actin or microtubules, appear to be req uired for tumor cell adhesion and its stabilization under hydrodynamic cond itions of fluid flow.