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  • Cytokeratin 8 ectoplasmic domain binds urokinase-type plasminogen activator to breast tumor cells and modulates their adhesion, growth and invasiveness
    Obermajer, Nataša ; Doljak, Bojan ; Kos, Janko, 1959-
    Background Generation of plasmin is a characteristic of tumor cells, promoting the degradation of extracellular matrix, tumor progression and metastasis. The process is accelerated if plasminogen and ... plasminogen activator are bound to their cell surface receptors. Results In this study weshow that the monoclonal antibody that recognizes an epitope on the cytokeratin 8 (CK8) ectoplasmic domain (anti-CK MAb) inhibits plasminogen activation mediated by urokinase-type plasminogen activator (uPA) in MCF-7 andMCF-10A neoT cells. The ectoplasmic domain of CK8 acts as a binding site for plasminogen, however, by using confocal microscopy, we demonstrated that it is also co-localized with uPA. CK8, therefore, functions also as a receptorfor uPA on the cell surface, and the presence of anti-CK MAb may prevent the binding of uPA to a designated CK8 motif. The consequent inhibition of plasmin generation resulted in changed cell morphology, enhancedcell adhesion to fibronectin, reduced invasion potential, and an enhanced G1/S transition. Moreover, surface plasmon resonance analysis showed that the synthetic dodecapeptide corresponding to the epitope sequence (VKIALEVEIATY), binds uPA in the nanomolar range. Conclusions These novel findings suggest a model in which CK8, together with uPA, plasminogen and fibronectin, constitutes a signaling platform capable of modulating cell adhesion/growth-dependent signal transduction in breast tumor cells. Anti-CK MAb, which competes for the binding site for uPA, could be used as an agent toreduce the invasive potential of breast tumor cells.
    Vir: Molecular cancer [Elektronski vir]. - ISSN 1476-4598 (vol. 8, no. 88, 2009, 31 str.)
    Vrsta gradiva - e-članek
    Leto - 2009
    Jezik - angleški
    COBISS.SI-ID - 2696561

    Povezava(-e):

    http://www.molecular-cancer.com/content/8/1/88
    DOI

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