Prostate cancer induces C/EBPβ expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcome

Prostate. 2019 Apr;79(5):435-445. doi: 10.1002/pros.23749. Epub 2018 Dec 11.

Abstract

Background: Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating adaptations in the tumor-bearing organ. Similar changes are seen in prostate cancer patients and they are related to outcome. One gene previously found to be upregulated in the non-malignant part of tumor-bearing prostate lobe in rats was the transcription factor CCAAT/enhancer-binding protein-β (C/EBPβ).

Methods: To explore this further, we examined C/EBPβ expression by quantitative RT-PCR, immunohistochemistry, and Western blot in normal rat prostate tissue surrounding slow-growing non-metastatic Dunning G, rapidly growing poorly metastatic (AT-1), and rapidly growing highly metastatic (MatLyLu) rat prostate tumors-and also by immunohistochemistry in a tissue microarray (TMA) from prostate cancer patients managed by watchful waiting.

Results: In rats, C/EBPβ mRNA expression was upregulated in the surrounding tumor-bearing prostate lobe. In tumors and in the surrounding non-malignant prostate tissue, C/EBPβ was detected by immunohistochemistry in some epithelial cells and in infiltrating macrophages. The magnitude of glandular epithelial C/EBPβ expression in the tumor-bearing prostates was associated with tumor size, distance to the tumor, and metastatic capacity. In prostate cancer patients, high expression of C/EBPβ in glandular epithelial cells in the surrounding tumor-bearing tissue was associated with accumulation of M1 macrophages (iNOS+) and favorable outcome. High expression of C/EBPβ in tumor epithelial cells was associated with high Gleason score, high tumor cell proliferation, metastases, and poor outcome.

Conclusions: This study suggest that the expression of C/EBP-beta, a transcription factor mediating multiple biological effects, is differentially expressed both in the benign parts of the tumor-bearing prostate and in prostate tumors, and that alterations in this may be related to patient outcome.

Keywords: C/EBPβ; biomarkers; prostate cancer; tumors instruct adjacent tissues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CCAAT-Enhancer-Binding Protein-beta / biosynthesis*
  • CCAAT-Enhancer-Binding Protein-beta / genetics
  • Cell Growth Processes / physiology
  • Cohort Studies
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • ErbB Receptors / metabolism
  • Humans
  • Immunohistochemistry
  • Male
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Phosphorylation
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology*
  • Protein Isoforms
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Tissue Array Analysis

Substances

  • CCAAT-Enhancer-Binding Protein-beta
  • Protein Isoforms
  • RNA, Messenger
  • EGFR protein, human
  • Egfr protein, rat
  • ErbB Receptors