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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Marchisio, P. C. Besati, C. Cecchini, G. Ambesi-impiombato, F. S. Trusolino, L. Serini, G. De Filippi, R. |
| Description | Author Affiliation: Trusolino L ( DIBIT, Department of Biological and Technological Research, San Raffaele Scientific Institute, 20132 Milano, Italy.) |
| Abstract | Integrin activation is a multifaceted phenomenon leading to increased affinity and avidity for matrix ligands. To investigate whether cytokines produced during stromal infiltration of carcinoma cells activate nonfunctional epithelial integrins, a cellular system of human thyroid clones derived from normal glands (HTU-5) and papillary carcinomas (HTU-34) was employed. In HTU-5 cells, αvβ3 integrin was diffused all over the membrane, disconnected from the cytoskeleton, and unable to mediate adhesion. Conversely, in HTU-34 cells, αvβ3 was clustered at focal contacts (FCs) and mediated firm attachment and spreading. αvβ3 recruitment at FCs and ligand-binding activity, essentially identical to those of HTU-34, occurred in HTU-5 cells upon treatment with hepatocyte growth factor/scatter factor (HGF/SF). The HTU-34 clone secreted HGF/SF and its receptor was constitutively tyrosine phosphorylated suggesting an autocrine loop responsible for αvβ3 activated state. Antibody-mediated inhibition of HGF/SF function in HTU-34 cells disrupted αvβ3 enrichment at FCs and impaired adhesion. Accordingly, activation of αvβ3 in normal cells was produced by HTU-34 conditioned medium on the basis of its content of HGF/SF. These results provide the first example of a growth factor–driven integrin activation mechanism in normal epithelial cells and uncover the importance of cytokine-based autocrine loops for the physiological control of integrin activation. |
| ISSN | 00219525 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 4 |
| Volume Number | 142 |
| Language | English |
| Publisher | Rockefeller University Press (United States) |
| Publisher Date | 1998-08-24 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Antigens, CD Metabolism Cell Adhesion Physiology Cytokines Hepatocyte Growth Factor Pharmacology Neoplasm Invasiveness Physiopathology Platelet Membrane Glycoproteins Antigens, CD29 Cell Movement Clone Cells Cytoskeleton Extracellular Matrix Flow Cytometry Fluorescent Antibody Technique Integrin Beta3 Neoplasm Metastasis Phosphorylation Proto-Oncogene Proteins C-met Signal Transduction Thyroid Gland Tumor Cells, Cultured Tyrosine Research Support, Non-U.S. Gov't Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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