Prostate Cancer Cell Surface-Associated Keratin 8 and Its Implications for Enhanced Plasmin Activity |
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Authors: | Melissa Hirsch Kuchma Joo Hee Kim Mark T Muller Philip A Arlen |
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Institution: | (1) Cancer Research Institute, MD Anderson Cancer Center Orlando, 6900 Lake Nona Blvd, Orlando, FL 32827, USA;(2) Department of Molecular Biology and Microbiology, University of Central Florida College of Medicine, 12722 Research Parkway, Orlando, FL 32826, USA;(3) Present address: Department of Molecular Biology and Microbiology, University of Central Florida College of Medicine, 12722 Research Parkway, Orlando, FL 32826, USA |
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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. |
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