| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
¶
From the Departments of Pathology* and Urology, University Medical Center ‘St. Radboud,’ Nijmegen, The Netherlands; and the Department of Pathology, the Brady Urological Institute, and the Sidney Kimmel Comprehensive Cancer Center,¶ The Johns Hopkins University, School of Medicine, Baltimore Maryland
Within the human prostate epithelium four cell populations can be discriminated based on their expression of keratins (K). Basal cells express high levels of K5 and K14, as well as p63, whereas they have very low levels of androgen receptor, prostate-specific antigen (PSA), K8, and K18. Luminal secretory cells lack p63, K5, and K14 but express high levels of K8, K18, androgen receptor, and PSA. Additionally, cells have been identified with a keratin phenotype intermediate between basal and luminal cells that co-express high levels of K5 and K18 (K5/18) as well as hepatocyte growth factor receptor c-MET. Although intermediate cells have been proposed as precursor cells of prostate cancer, their biology is ill defined. Epithelial cells in proliferative inflammatory atrophy (PIA) appear to be cycling rapidly as indicated by expression of Ki-67, and morphological transitions have been identified between PIA and high-grade prostate intraepithelial neoplasia. Many of the atrophic epithelial luminal cells in PIA are candidates for intermediate cells based in part on weak expression of PSA and androgen receptor, high levels of K8/18, and lack of p63. The objective of this study was to further clarify the phenotype of the proposed intermediate cells in PIA and to quantitatively determine the level in which these intermediate cells preferentially occur in PIA lesions. Intermediate cells were immunohistochemically demonstrated using antibodies to K5, K14, K18, and c-MET. Using radical prostatectomy specimens (n = 15) the area fraction of intermediate cells in normally differentiated prostate epithelium and PIA were quantified by a grid point counting method. Atrophic luminal cells of PIA lesions expressed K5 in 39.2 ± 7.4% of cells compared to 2.4 ± 2.3% in normal epithelium (P < 0.00001). By contrast, K14 was only expressed in 3.0 ± 3.2% of the luminal cells. Previous studies have shown that virtually 100% of these atrophic luminal cells are strongly positive for K8/18. c-MET was present in 44.1 ± 14.1% of luminal cells in PIA but only in 2.1 ± 2.8% of luminal cells in normal epithelium (P < 0.00001). To unambiguously determine whether intermediate luminal cells in PIA show increased proliferative activity and decreased p27kip1 expression, double-staining immunofluorescence of Ki-67 and K5, as well as p27Kip1 and K5 was performed. Luminal cells in PIA often co-expressed K5 and Ki-67. Although p27Kip1 was strongly expressed in K5-negative differentiated cells in normal epithelium, p27Kip1 staining was absent in many of the K5-positive cells in the luminal compartment of PIA. We conclude that cells phenotypically intermediate between basal and secretory cells are enriched in PIA lesions. The finding of a large number of highly proliferating intermediate cells in PIA provides further support that these cells may serve as preferred target cells in prostate carcinogenesis.
This article has been cited by other articles:
 |
|
 |
|
  N. J. Maitland and A. T. Collins Prostate Cancer Stem Cells: A New Target for Therapy J. Clin. Oncol., June 10, 2008; 26(17): 2862 - 2870. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mimeault, P. P. Mehta, R. Hauke, and S. K. Batra Functions of Normal and Malignant Prostatic Stem/Progenitor Cells in Tissue Regeneration and Cancer Progression and Novel Targeting Therapies Endocr. Rev., April 1, 2008; 29(2): 234 - 252. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Das, K. Wojno, and M. J. Imperiale BK Virus as a Cofactor in the Etiology of Prostate Cancer in Its Early Stages J. Virol., March 15, 2008; 82(6): 2705 - 2714. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Letellier, M.-J. Perez, M. Yacoub, P. Levillain, O. Cussenot, and G. Fromont Epithelial Phenotypes in the Developing Human Prostate J. Histochem. Cytochem., September 1, 2007; 55(9): 885 - 890. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. Bethel, D. Faith, X. Li, B. Guan, J. L. Hicks, F. Lan, R. B. Jenkins, C. J. Bieberich, and A. M. De Marzo Decreased NKX3.1 Protein Expression in Focal Prostatic Atrophy, Prostatic Intraepithelial Neoplasia, and Adenocarcinoma: Association with Gleason Score and Chromosome 8p Deletion. Cancer Res., November 15, 2006; 66(22): 10683 - 10690. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. V. Litvinov, D. J. Vander Griend, Y. Xu, L. Antony, S. L. Dalrymple, and J. T. Isaacs Low-Calcium Serum-Free Defined Medium Selects for Growth of Normal Prostatic Epithelial Stem Cells. Cancer Res., September 1, 2006; 66(17): 8598 - 8607. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Bianco, S. J. McPherson, H. Wang, G. S. Prins, and G. P. Risbridger Transient Neonatal Estrogen Exposure to Estrogen-Deficient Mice (Aromatase Knockout) Reduces Prostate Weight and Induces Inflammation in Late Life Am. J. Pathol., June 1, 2006; 168(6): 1869 - 1878. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mimeault and S. K. Batra Recent advances on multiple tumorigenic cascades involved in prostatic cancer progression and targeting therapies Carcinogenesis, January 1, 2006; 27(1): 1 - 22. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Dalrymple, L. Antony, Y. Xu, A. R. Uzgare, J. T. Arnold, J. Savaugeot, L. J. Sokoll, A. M. De Marzo, and J. T. Isaacs Role of Notch-1 and E-Cadherin in the Differential Response to Calcium in Culturing Normal versus Malignant Prostate Cells Cancer Res., October 15, 2005; 65(20): 9269 - 9279. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C Hughes, A Murphy, C Martin, O Sheils, and J O'Leary Molecular pathology of prostate cancer J. Clin. Pathol., July 1, 2005; 58(7): 673 - 684. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. S. Knudsen, J. M. Lucas, L. Fazli, S. Hawley, S. Falcon, I. M. Coleman, D. B. Martin, C. Xu, L. D. True, M. E. Gleave, et al. Regulation of Hepatocyte Activator Inhibitor-1 Expression by Androgen and Oncogenic Transformation in the Prostate Am. J. Pathol., July 1, 2005; 167(1): 255 - 266. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G Bidaux, M Roudbaraki, C Merle, A Crepin, P Delcourt, C Slomianny, S Thebault, J-L Bonnal, M Benahmed, F Cabon, et al. Evidence for specific TRPM8 expression in human prostate secretory epithelial cells: functional androgen receptor requirement Endocr. Relat. Cancer, June 1, 2005; 12(2): 367 - 382. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Atanassova, C. McKinnell, J. Fisher, and R. M Sharpe Neonatal treatment of rats with diethylstilboestrol (DES) induces stromal-epithelial abnormalities of the vas deferens and cauda epididymis in adulthood following delayed basal cell development Reproduction, May 1, 2005; 129(5): 589 - 601. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. Hofer, R. Kuefer, S. Varambally, H. Li, J. Ma, G. I. Shapiro, J. E. Gschwend, R. E. Hautmann, M. G. Sanda, K. Giehl, et al. The Role of Metastasis-Associated Protein 1 in Prostate Cancer Progression Cancer Res., February 1, 2004; 64(3): 825 - 829. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
