00085472can142465-sup-136645_1_supp_2792249_ngsl4f.pptx (148.33 MB)

Supplemental Figures S1-S7 from Hepcidin Regulation in Prostate and Its Disruption in Prostate Cancer

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posted on 2023-03-30, 23:07 authored by Lia Tesfay, Kathryn A. Clausen, Jin Woo Kim, Poornima Hegde, Xiaohong Wang, Lance D. Miller, Zhiyong Deng, Nicole Blanchette, Tara Arvedson, Cindy K. Miranti, Jodie L. Babitt, Herbert Y. Lin, Donna M. Peehl, Frank M. Torti, Suzy V. Torti

Supplemental Figures S1-S7. Hepcidin transcript levels in prostate cells under basal conditions and in response to modulation by signaling effectors (S1); Immunohistochemical detection of hepcidin in prostate tissue (S2); Clonegenic survival of DU145 cells treated with DFO (S3); BMPs induce SMAD signaling in prostate cancer cells (S4); Effect of BMP6 and BMP7 on hepcidin in PC3 and LNCaP prostate cancer cells (S5); Effect of Wnt pathway agonists or antagonists in DU145 cells (S6); Immunohistochemical detection of SOSTDC1 in prostate tissue (S7).

History

ARTICLE ABSTRACT

Hepcidin is a circulating peptide hormone made by the liver that is a central regulator of systemic iron uptake and recycling. Here, we report that prostate epithelial cells also synthesize hepcidin, and that synthesis and secretion of hepcidin are markedly increased in prostate cancer cells and tissue. Prostatic hepcidin functions as an autocrine hormone, decreasing cell surface ferroportin, an iron exporter, increasing intracellular iron retention, and promoting prostate cancer cell survival. Synthesis of hepcidin in prostate cancer is controlled by a unique intersection of pathways that involves BMP4/7, IL6, Wnt, and the dual BMP and Wnt antagonist, SOSTDC1. Epigenetic silencing of SOSTDC1 through methylation is increased in prostate cancer and is associated with accelerated disease progression in patients with prostate cancer. These results establish a new connection between iron metabolism and prostate cancer, and suggest that prostatic dysregulation of hepcidin contributes to prostate cancer growth and progression. Cancer Res; 75(11); 2254–63. ©2015 AACR.