Intermediate cells in normal and malignant prostate epithelium express c-MET: implications for prostate cancer invasion

Prostate. 2002 May 1;51(2):98-107. doi: 10.1002/pros.10073.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgens / pharmacology
  • Carcinoma / genetics
  • Carcinoma / pathology*
  • Cell Differentiation
  • Cell Transformation, Neoplastic
  • Epithelial Cells
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Male
  • Neoplasm Invasiveness*
  • Prostate / cytology
  • Prostate / physiology*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology*
  • Proto-Oncogene Proteins c-met / biosynthesis*


  • Androgens
  • Proto-Oncogene Proteins c-met