Activation status and function of the VLA-4 (alpha4beta1) integrin expressed on human melanoma cell lines.
We have examined the functional status of the VLA-4/alpha4beta1 integrin in a panel of human melanoma cell lines, focusing on the ability of cells expressing alpha4beta1 to mediate adhesion to the alpha4-specific ligands CS-1 peptide and VCAM-1. All melanoma cells expressing alpha4pbeta1 (8 of 10 lines examined) were capable of adhering to these specific ligands in adhesion assays, whereas 2 cell lines (HMB2 and VUP) which lacked surface alpha4 were unable to do so. Adherence of different melanoma cell lines to VCAM-1 was relatively uniform and not susceptible to upregulation with known integrin-activating factors, such as manganese ions, phorbol ester and activating monoclonal antibody (mAb) TS2/16. Cell adhesion to CS-1 peptide, however, varied according to cell surface receptor density and, in some cases, could be up-regulated by integrin-activating factors. Adhesion of SK23 cells to CS-1 peptide was increased by all 3 activating stimuli, whereas for all other melanoma cells an increase was obtained only by the use of TS2/16 mAb. Our data indicate not only an unusually low activation state of alpha4beta1 in SK23 cells but also heterogeneity in the activating capacity of the various stimuli. Moreover, a protein kinase C-dependent role in alpha4beta1 activity was suggested by adhesion assays carried out in the presence of the protein kinase C inhibitor calphostin C, which considerably reduced adhesion to CS-1 peptide.
Saini
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Richard Dimbleby Department of Cancer Research/ICRF Laboratory, St. Thomas' Hospital, London, UK.
Seller
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Davies
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Marshall
J F
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Hart
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D018926:Anti-Allergic Agents / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism*; D014408:Biomarkers, Tumor; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000378:metabolism*; D008545:Melanoma / Q000276:immunology / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008840:Microfilament Proteins; D009281:Naphthalenes / Q000494:pharmacology; D011233:Precipitin Tests; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism*; D012208:Rhabdomyosarcoma / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D018926:Anti-Allergic Agents; D000954:Antigens, Surface; D014408:Biomarkers, Tumor; D004791:Enzyme Inhibitors; C482653:ITPRID2 protein, human; D039041:Integrin alpha4beta1; D016023:Integrins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009281:Naphthalenes; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; D011493:Protein Kinase C; C058819:calphostin C