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- Title
Evidence of the Involvement of Phosphatidylinositol 3-Kinase in the Migration, Actin Stress Fiber Formation, and α<sub>v</sub>β<sub>3</sub>-Integrin-Mediated Adherence of Human Melanoma Cells.
- Authors
Metzner, Beatrix; Barbisch, Michael; Bachmann, Felix; Czech, Wolfgang; Norgauer, Johannes
- Abstract
Tumor invasion and formation of metastases are major obstacles for a successful therapy of melanomas. Metastasis is thought to require multiple steps such as αvbeta;3 3-integrin-mediated adhesion, proteolytic digestion of extracellular matrix by metalloproteinase-2, and reorganization of the actin cytoskeleton. To analyze the functional role of phosphatidylinositol 3-kinase in these processes, melanoma cells were treated with the fungal metabolite wortmannin. Wortmannin inhibited phosphatidylinositol 3-kinase activity in melanoma cells and migration in an equally concentration-dependent fashion, Flow cytometric analysis of <em>N</em>-(7-nitrobenz-2-oxa-1,3-diazol-4- y1)phallacidin-stained actin network indicated reduction of actin filaments by wortmannin. Fluorescence laser confocal microscopy experiments revealed breakdown of actin stress fibers. In addition, wortmannin inhibited αvβ3-integrin-mediated adhesion of melanoma cells to vitronectin, Since flow cytometic measurements did not show altered expression of the αvβ3-integrin at the cell surface, avidity changes of the αvβ3-integrin by wortmannin are suggested. In contrast to the actin analysis and adhesion assays, wortmannin had no influence on mRNA expression or on protein secretion of metalloproteinase-2. These data provide evidence that phosphatidylinositol 3-kinase is an essential signal transduction protein required for migration of melanoma cells, regulating formation of the actin stress fiber as well as αvβ3- integrin-mediated adhesion.
- Publication
Journal of Investigative Dermatology, 1996, Vol 107, Issue 4, p597
- ISSN
0022-202X
- Publication type
Academic Journal
- DOI
10.1111/1523-1747.ep12583096