Locomotion of tumor cells: a molecular comparison to migrating pre- and postmitotic leukocytes

Increasing evidence has shown that the molecular regulation of active cell migration of slow-moving cells, e.g., tumor cells and fibroblasts, is diffe rent from fast-moving leukocytes, e.g., T lymphocytes and neutrophil granul ocytes. Slow-moving cells develop focal adhesions as a crucial regulatory e lement during migration. These focal adhesions connect the extracellular ma trix to the intracellular actin- and tubulin-cytoskeleton via integrins and enzymatically active proteins. Beside matrix-binding integrins, ligands of receptor tyrosine kinases and heterotrimeric G protein-coupled serpentine receptors initiate migration of slow-moving cells. Focal adhesions are not found in T lymphocytes and neutrophil granulocytes moving within three-dime nsional matrices. In T lymphocytes, the T cell receptor is supposed to have a key regulatory function not only in antigen recognition, cell activation , and proliferation but also in cell migration. Regulatory molecules as wel l as the cytoskeleton are connected to the T cell receptor. The T cell rece ptor functionally combines elements of receptor tyrosine kinase signaling a nd of focal adhesions. In neutrophil granulocytes no multi-protein complexe s regulating migration have been identified so far. Most potent activators of migration of neutrophil granulocytes, as those of T lymphocytes, are che mokines binding to heterotrimeric G protein-coupled serpentine receptors.