Correlative human studies suggest that the pleiotropic cytokine interleukin-6 (IL-6) contributes to the development and/or progression of prostate cancer. However, the source of IL-6 production in the prostate microenvironment in patients has yet to be determined. The cellular origin of IL-6 in primary and metastatic prostate cancer was examined in formalin-fixed, paraffin-embedded (FFPE) tissues using a highly sensitive and specific chromogenic in situ hybridization (CISH) assay that underwent extensive analytical validation. Quantitative RT-PCR (q-RT-PCR) showed that benign prostate tissues often had higher expression of IL-6 mRNA than matched tumor specimens. CISH analysis further indicated that both primary and metastatic prostate adenocarcinoma cells do not express IL-6 mRNA. IL-6 expression was highly heterogeneous across specimens and was nearly exclusively restricted to the prostate stromal compartment - including endothelial cells and macrophages among other cell types. The number of IL-6-expressing cells correlated positively with the presence of acute inflammation. In metastatic disease, tumor cells were negative in all lesions examined and IL-6 expression was restricted to endothelial cells within the vasculature of bone metastases. Finally, IL-6 was not detected in any cells in soft tissue metastases. These data suggest that, in prostate cancer patients, paracrine rather than autocrine IL-6 production is likely associated with any role for the cytokine in disease progression.
- Received January 14, 2015.
- Revision received May 10, 2015.
- Accepted May 26, 2015.
- Copyright © 2015, American Association for Cancer Research.