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Intermediate cells in normal and malignant prostate epithelium express c-MET: implications for prostate cancer
Geert van Leenders1, Bianca van Balken, Tilly Aalders
1Department of Pathology, University Medical Center St. Radboud, PO Box 9101, 6500 HB Nijmegen, The Netherlands. G.vanleenders@pathol.azn.nl
Background:
Analysis of keratin (K) expression discriminates luminal (K18) and intermediate (K5/18) cells in prostate carcinoma, while basal (K5/14) cells are absent. Intermediate cells have been proposed as targets of malignant transformation in prostate cancer and precursors of androgen-independent tumor progression. We demonstrate localization of hepatocyte growth factor (HGF) receptor c-MET in intermediate cells in both normal and malignant prostate epithelium.
Methods:
Receptor localization was analyzed using triple staining for c-MET, K5, K14, and K18. The percentage of strongly c-MET positive cells was determined in 15 prostate cancer patients undergoing androgen-deprivation and 14 patients without neo-adjuvant treatment. Effects of HGF were investigated on prostate cancer cell line DU145.
Results:
c-MET expression in non-malignant epithelium was strong in intermediate cells absent in differentiated cells, and heterogeneous in basal cells. In prostate cancer, intermediate cells displayed high c-MET levels coupled with mild expression in differentiated cells. During androgen-deprivation, 7.6% of tumor cells revealed high c-MET expression compared to 1.7% without treatment (P = 0.02). Matrigel penetration of DU145 was 8.2 +/- 1.7 mm(2) after HGF stimulation compared to 3.6 +/- 2.4 mm(2) in controls (P < 0.02).
Conclusions:
Intermediate cells in normal and malignant prostate epithelium express high c-MET levels, indicating that they are prone to stromal invasion in prostate carcinoma.