Loss of CD10 (neutral endopeptidase) is a frequent and early event in human prostate cancer

Prostate. 2003 Apr 1;55(1):71-80. doi: 10.1002/pros.10202.

Abstract

Background: We hypothesized that the aggressive LNCaP-derived androgen-independent cell line, CL1, might differ from LNCaP in their repertoire of cell surface markers and that these differences might typify changes that occur during clinical prostate cancer progression.

Methods: The cell surface marker expression profiles of CL1 and LNCaP were examined using flow cytometry. Markedly differential gene expression was confirmed using RT-PCR and further examined using immunohistochemistry among the prostate cancer cell lines LAPC-4, LNCaP, CL1, CL2, DU145, and PC-3. The expression of the most markedly differentially expressed surface marker, CD10, was further explored in a tissue microarray containing radical prostatectomy samples from 219 hormone naïve prostate cancer patients.

Results: There were marked differences in the expression of CD10, CD13, CD26, CD33, CD44, CD54, CD55, and CD104 between CL1 and LNCaP. Results from both the RT-PCR and immunohistochemistry confirmed the differential expression and found that CD10 demonstrated a pattern of expression in hormone sensitive but not hormone refractory cell lines. When CD10 expression was examined in a tissue microarray, CD10 expression was below the 25th percentile of matched normal prostate tissue in 68% of prostate cancers, below the median expression of matched normal prostate tissue in 86% of cancers, and completely absent in 34% of cancers. Samples of prostatic intraepithelial neoplasia demonstrated CD10 expression that was intermediate between normal prostatic tissue and prostate cancer. Among prostate cancer patients, CD10 expression did not correlate with Gleason score, pathological stage, or biochemical recurrence following radical prostatectomy.

Conclusions: These findings demonstrate that loss or decreased expression of CD10 is an early and frequent event in human prostate cancer and implicates CD10 as a potential therapeutic target for early stage hormone sensitive prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Flow Cytometry
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasms, Hormone-Dependent / enzymology
  • Neoplasms, Hormone-Dependent / genetics
  • Neoplasms, Hormone-Dependent / pathology
  • Neprilysin / biosynthesis*
  • Neprilysin / genetics
  • Prostatic Neoplasms / enzymology*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology
  • Protein Array Analysis
  • RNA, Neoplasm / biosynthesis
  • RNA, Neoplasm / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured

Substances

  • RNA, Neoplasm
  • Neprilysin