Actin-dependent tumour cell adhesion after short-term exposure to the antimetastasis ruthenium complex NAMI-A.
Imidazolium trans-imidazoledimethylsulphoxidetrachlororuthenate (NAMI-A) was tested in vitro on the pro-adhesive properties, evaluated as resistance to trypsin treatment, which is a bona fide measure of adhesion strength, of KB and HeLa carcinoma cell lines and on human polymorphonuclear neutrophils (HPMN). NAMI-A increased the pro-adhesive activity of KB cells at 0.001 mM concentration, after few minutes incubation and this effect was not influenced by the vehicle used for cell challenge, neither did it depend on NAMI-A concentration or on temperature. The same effect occurred on HeLa cells at 0.01 mM NAMI-A. This effect, detected at concentrations up to 100 times lower than those necessary to block cells at the G(2)-M premitotic phase of cell cycle, or to inhibit matrix metalloproteinase release or cell invasion, was not related to ruthenium uptake by tumour cells. HeLa cells and healthy HPMN, following short exposure to 0.1 mM NAMI-A, assumed a different shape, with the extrusion of filopodia (HeLa) and of large lamellopodia (HPMN), which increased their interactions with the substrate. This effect was attributed to stabilisation, altered turnover and sensitivity to cytochalasin D of actin filaments. Provided that adhesion is associated with cell motility and invasion, these data suggest that NAMI-A may exert antimetastatic properties at concentrations lower than those observed in the lungs at the end of a conventional intraperitoneal treatment in vivo.
Sava
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Department of Biomedical Sciences, University of Trieste, Via L. Giorgieri 7, 34127 Trieste, Italy. g.sava@callerio.org
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Cocchietto
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Vita
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Podda
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Spessotto
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Furlani
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Scarcia
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Zabucchi
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D008841:Actin Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D019138:Antibodies, Blocking / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000032:analysis / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D004121:Dimethyl Sulfoxide / Q000031:analogs & derivatives* / Q000032:analysis / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D016023:Integrins / Q000276:immunology; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009504:Neutrophils / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D009942:Organometallic Compounds / Q000032:analysis / Q000494:pharmacology*; D012428:Ruthenium / Q000032:analysis; D017975:Ruthenium Compounds; D014357:Trypsin
D019138:Antibodies, Blocking; D000970:Antineoplastic Agents; D016023:Integrins; D009942:Organometallic Compounds; D017975:Ruthenium Compounds; C113661:imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III); D012428:Ruthenium; D014357:Trypsin; D004121:Dimethyl Sulfoxide