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Agonists and antagonists of the collagen-binding integrins a1b1 and a2b1 and their effects on cell contacts with the basement membrane and the interstitial matrix
Antragsteller
Professor Dr. Johannes Andreas Eble
Fachliche Zuordnung
Dermatologie
Förderung
Förderung von 2000 bis 2008
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5247330
Integrins mediate contacts of cells with basal membrane components and other extracellular matrix (ECM) proteins, such as collagens and laminins. Among the collagen receptors, the two integrins a1ß1 and a2ß1 play a pivotal role in cell-matrix interaction. Recombinant soluble ectodomain heterodimers of a1ß1 and a2ß1 integrins help to identify the recognition motifs within their collagen and non-collagenous ligands, and allow to screen phage display libraries for conformationally restricted peptide sequences which imitate a1ß1 and a2ß1 integrin ligands. Characterization of such peptide mimetics for both collagen-binding integrins would disclose molecular details of collagen recognition, such as essential functional groups and structural requirements. Furthermore, these peptide agonists/antagonists will be useful tools in identifying the effects of integrin-collagen interaction on cell proliferation, adhesion, and migration, as well as gene expression of metallo-matrix-proteases (MMPs). MMPs degrade collagen and basal membrane proteins thus enabling tumor cells to penetrate through the basal membrane, causing tumor invasion and metastasis.
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