Abstract LB-373: Elucidation of the mechanisms involved in IL-6 induced cell transformation in prostate cancer
Authors: Andres Rojas, Gavin Liu, Ilsa Colemen, Peter Nelson, Paul B. Fisher, Stephen R. Plymate, Jennifer Wu
Journal: Cancer Research (2010)

Abstract Background: Prostate cancer is the most common non-cutaneous malignant neoplasm in men in Western countries. Several studies have shown a significant correlation between the formation of a tumor and chronic prostatic inflammation, generally triggered by infectious agents or exposure to environmental factors (smoking, alcohol, burned meat, etc.), and/or various combination thereof. The incidence of chronic inflammation of the prostate is associated with the presence of inflammatory cells involved in the secretion of cytokines, which promote the migration and proliferation of cells implicated in the immune response. Our main objective of this project is to elucidate the mechanism involved in the promotion of prostate cancer mediated by IL-6 using different approaches such as Western Blots, qPCR, luciferase based reporter assays and immunofluorescence. Results: The effects of cytokines on prostate epithelial cells are not well understood, however some evidence showed that its presence may play a role in the initiation of prostate cancer of patients with chronic prostate inflammation. Preliminary data generated in our laboratory have shown that when the prostate cell lines p69 and BPH-1 (non- tumorigenic prostate cell lines) are treated with the cytokines IL-6 and TNF-α, their proliferation rate is higher when compared with non-treated cells. In addition we have observed that P69 cells cultured in presence of IL-6 suffer significant changes in their morphology as well as changes in the distribution of E-cadherin in the cell membrane. The activation of the MAPK pathway also was detected after the cytokine treatment but when we used the MAPK inhibitors (LY294002 and PD98059) the expression levels of E-cadherin and Vimentin were closed to those observed on non-treated cells. Previous reports have shown that the Snail transcription factor is involved in the regulation of the expression of E-cadherin and Vimentin. Interestingly, we have detected this transcription higher levels of this transcription factor (mRNA as well as protein) after stimulation of p69 and BPH-1 cells with IL-6. The presence of this transcription factor was not noticed in non-treated cells. Finally, we have performed a luciferase based assay to establish the occurrence of cell transformation and we have found a higher activation of the luciferase reporter in these cells when they were treated with IL-6. Interestingly, when we block the activity of the IGF-IR using the antibody A12, we have a reduction of the EMT phenotype observed in cells that were treated only with IL-6. Low effects of the antibody were detected in non-treated cells. It is possible that such modifications might help to facilitate epithelial cell invasion into the stromal and vasculature compartments. In summary, we are showing novel mechanisms by which IL-6 may play a key role in the initiation of prostate cancer in patients with chronic prostate inflammation. To have a better understanding of this event may help in the early treatment of this type of cancer. Further “in vivo” experiments will be performed to establish the importance of IL-6 in the development of tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-373.