Metalloreductase STEAP1, also known as Six-Transmembrane Epithelial Antigen of Prostate 1 (STEAP1), is a protein that plays a significant role in metal ion metabolism. It is part of the STEAP family, which includes STEAP1, STEAP2, STEAP3, and STEAP4. These proteins are unique to mammals and share an innate activity as metalloreductases, indicating their importance in metal metabolism .
STEAP1 is characterized by its six-transmembrane domain structure, with both the N-terminal and C-terminal located on the cytoplasmic side . Unlike other members of the STEAP family, STEAP1 lacks the innate metalloreductase activity conferred by the presence of the FNO-like domain . However, it still plays a crucial role in cellular processes due to its structural features.
STEAP1 is involved in the uptake of iron and copper, facilitated by two conserved histidine residues predicted to bind at least one intramembrane heme group . It actively increases intra- and intercellular communication through the modulation of sodium (Na+), calcium (Ca2+), and potassium (K+) concentrations, as well as the concentration of small molecules . This modulation is essential for various cellular processes, including cell proliferation and apoptosis.
STEAP1 is overexpressed in several types of human cancers, including prostate, bladder, colon, pancreas, ovary, testis, breast, cervix, and Ewing sarcoma . Its overexpression is associated with poor prognosis and increased tumor invasiveness . Due to its localization in the cell membrane and differential expression in normal and cancer tissues, STEAP1 is considered a potential target for cancer immunotherapy .
The mouse anti-human STEAP1 antibody is a monoclonal antibody that specifically targets the human STEAP1 protein. This antibody is used in various research applications, including Western blotting (WB), immunohistochemistry (IHC), and immunofluorescence (IF) . It is particularly useful in studying the expression and function of STEAP1 in human cancer cells.
Research has shown that targeting STEAP1 with chimeric antigen receptor (CAR) T cell therapy can be an effective strategy against advanced prostate cancer . Studies in immunodeficient mice have demonstrated substantial antitumor activity, highlighting the potential of STEAP1 as a therapeutic target . Additionally, the combination of STEAP1 vaccine and PD-1 blocking antibody has significantly improved survival in animal models .