Title

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

Authors

Authors

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

Comments

Authors: contact us about adding a copy of your work at STARS@ucf.edu

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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