title: Inhibition of melanoma cell directional migration in vitro via different cellular targets.
abstract: In malignant melanoma active movement of cancer cells is considered to be essential for tissue invasion. Various mechanisms, such as the Ca(2+)-calmodulin-proteinkinase C cascade or G-protein-dependent processes are considered to play a role in tumor cell functions. The assay of directional migration, combined with computer-assisted image analysis, was used to evaluate the antimigratory efficacy of drugs interfering with different steps of signal transduction pathways. Treatment with different compounds showed a more or less concentration-dependent reduction of migration rates: The Ca(2+)-channel blockers verapamil and devapamil showed a slight reduction of motility. The effect was more pronounced when the calmodulin antagonist flunarizine was used or the proteinkinase C inhibitors dequalinium, tamoxifen and H-7 were applied. A marked inhibition of motility was found with the G-protein antagonist L 651582. Thus, our results indicate that different signal transduction pathways are involved in the regulation of directional migration of K1735-M2 melanoma cells.
authors.affiliation: Department of Dermatology and Venerology, University of Graz, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Fink-Puches
authors.forename: C
authors.initials: C
authors.lastname: Helige
authors.forename: H
authors.initials: H
authors.lastname: Kerl
authors.forename: J
authors.initials: J
authors.lastname: Smolle
authors.forename: H A
authors.initials: HA
authors.lastname: Tritthart
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D003868:Dequalinium / Q000494:pharmacology; D005444:Flunarizine / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors; D007546:Isoquinolines / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013629:Tamoxifen / Q000494:pharmacology; D014230:Triazoles; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D014700:Verapamil / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D007546:Isoquinolines; D010879:Piperazines; D014230:Triazoles; D013629:Tamoxifen; D000620:Aminoimidazole Carboxamide; C062058:carboxyamido-triazole; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D014700:Verapamil; D003868:Dequalinium; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; C055885:devapamil; D005444:Flunarizine