STEAP3 blocking peptide

Iron is essential in cellular proliferation and survival based on its crucial roles in DNA and ATP synthesis. Tumor cells proliferate rapidly even in patients with low serum iron, although their actual mechanisms are not well known. To elucidate molecular mechanisms of efficient tumor progression under the hypoferric condition, we studied the roles of six-transmembrane epithelial antigen of the prostate family member 3 (STEAP3), which was reported to facilitate iron uptake. Using Raji cells with low STEAP3 mRNA expression, human STEAP3-overexpressing cells were established. The impact of STEAP3 expression was analyzed about the amount of iron storage, the survival under hypoferric conditions in vitro and the growth of tumor in vivo. STEAP3 overexpression increased ferritin, an indicator of iron storage, in STEAP3-overexpressing Raji cells. STEAP3 gave Raji cells the resistance to iron deprivation-induced apoptosis. These STEAP3-overexpressing Raji cells preserved efficient growth even in hypoferric mice, while parental Raji cells grew less rapidly. In addition, iron deficiency enhanced S7EAP3 mRNA expression in tumor cells. Furthermore, human colorectal cancer tissues exhibited more S7EAP3 mRNA expression and iron storage compared with normal colon mucosa. These findings indicate that STEAP3 maintains iron storage in human malignant cells and tumor proliferation under the hypoferric condition. (C) 2011 Elsevier Inc. All rights reserved.

Erythroid cells of the bone marrow, the most avid consumers of iron in the body, acquire ferric (Fe (3+)) iron exclusively via the transferrin cycling pathway. A long-standing fundamental molecular question of how ferric iron is handled in this pathway has been recently resolved by the identification of Steap3 (six-transmembrane epithelial antigen of the prostate 3) as an endosomal ferrireductase needed for efficient utilization of transferrin-delivered iron. Further characterization of Steap3 and other Steap proteins reveals a possible greater role of Steap proteins in iron and copper metabolism.