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Prostate cancer induces C/EBPβ expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcome
Author(s) -
Adamo Hanibal,
Hammarsten Peter,
Hägglöf Christina,
Dahl Scherdin Tove,
Egevad Lars,
Stattin Pär,
Halin Bergström Sofia,
Bergh Anders
Publication year - 2019
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.23749
Subject(s) - prostate cancer , prostate , immunohistochemistry , pathology , pca3 , medicine , tissue microarray , tumor progression , cancer research , cancer
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.