Prostate Cancer Cell Surface-Associated Keratin 8 and Its Implications for Enhanced Plasmin Activity

    Authors

    M. H. Kuchma; J. H. Kim; M. T. Muller;P. A. Arlen

    Comments

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    Abbreviated Journal Title

    Protein J.

    Keywords

    Prostate cancer; Keratin 8; Plasminogen; Plasminogen activator; Metastasis; Extracellular matrix; CYCLE-DEPENDENT EXPRESSION; BREAST-CARCINOMA CELLS; FOCAL ADHESION; KINASE; ACTIVATOR INHIBITOR-1; EPITHELIAL-CELLS; LUNG CARCINOMAS; TUMOR-CELLS; IN-VITRO; UROKINASE; RECEPTOR; Biochemistry & Molecular Biology

    Abstract

    Serum PSA, Gleason score, pathological stage, and positive surgical margins are currently used as predictors for disease recurrence. However, these criteria are less than precise in predicting disease outcome, with only 10% specificity at the 90% sensitivity level. Keratins are intermediate filament proteins that are contained within normal epithelia. However, human prostate cancer tissue shows differential immunohistochemical staining of keratin 8 (K8) when compared to normal prostate tissue. Our immunofluorescence and flow cytometry data show that K8 is also present on the cell surface of transformed prostate cancer cell lines. K8 is expressed at high levels on the surfaces of DU-145 and PC-3 cells but is expressed at comparatively lower levels on the surfaces of LNCaP cells, BPH-1 cells, and RWPE-1 cells. We hypothesize that extracellular K8 (eK8) present on epithelial prostate cancer cells plays an integral role in migration and in vivo dissemination. We found that K8 increased the rate of activity of plasmin approximately fivefold over a 48-h period. Functionally, K8 also enhanced the plasmin-mediated proteolysis of vitronectin, an important component of the prostate extracellular matrix. Taken together, our data show that K8 enhances the proteolytic activity of the plasminogen activation system, indicating that eK8 may be an important distinguishing marker in prostate cancer and progression.

    Journal Title

    Protein Journal

    Volume

    31

    Issue/Number

    3

    Publication Date

    1-1-2012

    Document Type

    Article

    Language

    English

    First Page

    195

    Last Page

    205

    WOS Identifier

    WOS:000301879700001

    ISSN

    1572-3887

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