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 different from fast-moving leukocytes, e.g., T lymphocytes and neutrophil granulocytes. Slow-moving cells develop focal adhesions as a crucial regulatory element during migration. These focal adhesions connect the extracellular matrix 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-dimensional 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 well as the cytoskeleton are connected to the T cell receptor. The T cell receptor functionally combines elements of receptor tyrosine kinase signaling and of focal adhesions. In neutrophil granulocytes no multi-protein complexes regulating migration have been identified so far. Most potent activators of migration of neutrophil granulocytes, as those of T lymphocytes, are chemokines binding to heterotrimeric G protein-coupled serpentine receptors.
Entschladen
F
F
Institute of Immunology, Witten/Herdecke University, Stockumer Strasse 10, 58448 Witten, Germany. frankent@uni-wh.de
Zänker
K S
KS
D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D002465:Cell Movement; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D008938:Mitosis; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D018925:Chemokines; D016207:Cytokines