Myosin regulation in the migration of tumor cells and leukocytes within a three-dimensional collagen matrix.
The migration of cells is a complex regulatory process which results in the generation of motor forces through the reorganization of the cytoskeleton. Here we present a comparative study of the expression and involvement of myosin in the regulation of the physiological migration of leukocytes and the pathological migration of tumor cells. We show that the involvement of myosin in the migration is distinct in these two cell types. In leukocytes, the activity of non-muscle myosin II is essential for both the spontaneous (matrix-induced) migration and the migration induced by ligands to G protein-coupled receptors, i.e. chemokines and neurotransmitters. In contrast, spontaneous tumor cell migration is largely independent of non-muscle myosin II activity, whereas the norepinephrine-induced migration is completely inhibited by either direct inhibition of non-muscle myosin II or of the kinases phosphorylating the myosin light chain, namely ROCK or the calcium/calmodulin-dependent myosin light-chain kinase.
Bastian
P
P
Institute of Immunology, Witten/Herdecke University, Stockumer Strasse 10, 58448 Witten, Germany.
Lang
K
K
Niggemann
B
B
Zaenker
K S
KS
Entschladen
F
F
D000199:Actins / Q000032:analysis; D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D003094:Collagen / Q000737:chemistry; D005260:Female; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D024462:Myosin Type II / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009219:Myosin-Light-Chain Kinase / Q000032:analysis / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D020033:Protein Isoforms / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured; D054460:rho-Associated Kinases
D000199:Actins; D006576:Heterocyclic Compounds, 4 or More Rings; D047908:Intracellular Signaling Peptides and Proteins; D020033:Protein Isoforms; C472645:blebbistatin; D003094:Collagen; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D009219:Myosin-Light-Chain Kinase; D024462:Myosin Type II; D009638:Norepinephrine