Positive association between cytoskeletal changes, melanoma cell attachment and invasion in vitro.
The literature concerning cytoskeletal changes and metastatic progression is unresolved, some studies suggesting a positive association between the ability of cells to organize their cytoskeleton and others suggesting an inverse correlation. In an attempt to learn more about cytoskeletal changes and the ability of melanoma cells to interact with extracellular matrix proteins we examined the effects of pharmacological manipulation of cell attachment and cell invasion through fibronectin on levels of F-actin and vimentin in a highly metastatic cutaneous melanoma cell line (A375-SM cells). Additionally, we examined whether any correlation existed between the levels of the cytoskeletal proteins and subpopulations of the cell line of varying invasive ability. We report that agents which reduced cell attachment to plastic and invasion through fibronectin in vitro (tamoxifen, N-desmethyltamoxifen and 17beta-oestradiol) caused increases in levels of F-actin and vimentin, whereas agents which did not affect attachment or invasion (4-hydroxytamoxifen and dihydrotestosterone) had little or no effect on the cytoskeletal proteins. In contrast, however, those cells which were most effective at invading through fibronectin were significantly better at acutely increasing their levels of F-actin and vimentin than less invasive cells. We speculate that the ability to rapidly and possibly reversibly alter the cytoskeleton might be associated with metastatically successful cells in vivo.
University of Sheffield Department of Medicine, Clinical Sciences Centre, Northern General Hospital, UK. s.l.mcginley@sheffield.ac.uk
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Dewhurst
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Rennie
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MacNeil
D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000235:genetics; D003599:Cytoskeleton / Q000502:physiology*; D013196:Dihydrotestosterone / Q000494:pharmacology; D054278:Embryonal Carcinoma Stem Cells; D004958:Estradiol / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D006801:Humans; D008544:Melanocytes / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure*; D008545:Melanoma / Q000235:genetics / Q000473:pathology* / Q000556:secondary / Q000648:ultrastructure; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure*; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology* / Q000648:ultrastructure; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014746:Vimentin / Q000096:biosynthesis / Q000235:genetics
D000199:Actins; D018931:Antineoplastic Agents, Hormonal; D003598:Cytoskeletal Proteins; D005353:Fibronectins; D012739:Gonadal Steroid Hormones; D009363:Neoplasm Proteins; D014746:Vimentin; D013196:Dihydrotestosterone; D013629:Tamoxifen; C016601:afimoxifene; D004958:Estradiol; C028787:N-desmethyltamoxifen