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Intermediate cells in normal and malignant prostate epithelium express c‐MET: Implications for prostate cancer invasion
Author(s) -
van Leenders Geert,
van Balken Bianca,
Aalders Tilly,
Hulsbergenvan de Kaa Christina,
Ruiter Dirk,
Schalken Jack
Publication year - 2002
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.10073
Subject(s) - du145 , prostate cancer , prostate , stromal cell , epithelium , cancer research , c met , hepatocyte growth factor , malignant transformation , androgen receptor , pathology , biology , medicine , cancer , lncap , receptor
Abstract 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. Prostate 51: 98–107, 2002. © 2002 Wiley‐Liss, Inc.