Integrin alpha sub(v) beta sub(3) mediates chemotactic and haptotactic motility in human melanoma cells through different signaling pathways
Distinctions between chemotaxis and haptotaxis of cells to extracellular matrix proteins have not been defined in terms of mechanisms or signaling pathways. Migration of A2058 human melanoma cells to soluble (chemotaxis) and substratum-bound (haptotaxis) vitronectin, mediated by alpha sub(v) beta su...
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Published in | The Journal of biological chemistry Vol. 271; no. 6; pp. 3247 - 3254 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
01.01.1996
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Online Access | Get full text |
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Summary: | Distinctions between chemotaxis and haptotaxis of cells to extracellular matrix proteins have not been defined in terms of mechanisms or signaling pathways. Migration of A2058 human melanoma cells to soluble (chemotaxis) and substratum-bound (haptotaxis) vitronectin, mediated by alpha sub(v) beta sub(3), provided a system with which to address these questions. Both chemotaxis and haptotaxis were completely inhibited by treatment with RGD-containing peptides. Chemotaxis was abolished by a blocking antibody by alpha sub(v) beta sub(3), (LM609), whereas haptotaxis was inhibited only by approximately 50%, suggesting involvement of multiple receptors and/or signaling pathways. However, blocking antibodies to alpha sub(v) beta sub(5), also present on A2058 cells, did not inhibit. Pertussis toxin treatment of cells inhibited chemotaxis by >80%, but did not inhibit haptotaxis. Adhesion and spreading over vitronectin induced the phosphorylation of paxillin on tyrosine. In cells migrating over substratum-bound vitronectin, tyrosine phosphorylation of paxillin increased 5-fold between 45 min and 5 h. Dilutions of anti- alpha sub(v) beta sub(3) that inhibited haptotaxis also inhibited phosphorylation of paxillin (by similar to 50%) and modestly reduced cell spreading. In contrast, soluble vitronectin did not induce tyrosine phosphorylation of paxillin. The data suggest that soluble vitronectin stimulates chemotaxis predominantly through a G protein-mediated pathway that is functionally linked to alpha sub(v) beta sub(3). Haptotaxis is analogous to directional cell spreading and requires arrow down dv beta sub(3)-mediated tyrosine phosphorylation of paxillin. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 content type line 23 ObjectType-Feature-1 |
ISSN: | 0021-9258 |