Background
STEAP2, also known as six transmembrane protein of prostate 1 (STAMP1), is a member of the metal-reducing enzyme family, which includes STEAP1, STEAP3, and STEAP4. This protein consists of 490 amino acids and features a structure composed of six transmembrane alpha helices along with hydrophilic N- and C-terminal domains. The N-terminal contains an intracellular FNO domain that binds NADPH, while the C-terminal includes a b-type heme-containing FRE domain. STEAP proteins are capable of reducing Fe3+ from transferrin-iron complexes that are endocytosed into the cell to Fe2+. The resulting Fe2+ is then stored in unstable iron pools and ferritin, with excess Fe2+ being oxidized back to Fe3+ by iron transport proteins to maintain intracellular iron homeostasis. Additionally, STEAP2 facilitates the reduction and uptake of Fe3+ within the cell.
Figure 1. Schematic structure of STEAP2
(Source: Rocha SM, et al. 2021)
STEAP2 is abundantly expressed in prostate tissue, most often in epithelial cell Golgi apparatus, the trans-Golgi network, and the plasma membrane. It is expressed, along with the prostate, in other normal human organs, including the heart, the colon, the pancreas, the uterus and the testes. There is a significant level of STEAP2 expression in human pluripotent bone marrow adherent cultures, and a notable upregulation of STEAP2 mRNA has been observed at the base of crypts in the human colon. Additionally, in mouse embryos, STEAP2 is strongly expressed in the epithelium of the gastro-duodenal junction, fetal liver, and choroid plexus.
We are currently studying STEAP2 only for tumours such as prostate cancer, breast cancer, gliomas, lung cancer and colon cancer. STEAP2 has the power to control tumour progression and growth through proliferation and death of cells, the immune microenvironment and immune invasion. For example, STEAP2 promotes the growth of prostate cancer cells via the extracellular signal-regulated kinase (ERK) system and regulates cell cycle genes that arrest the cell cycle, partial at G0-G1. Conversely, knocking down the STEAP2 gene increases the number of apoptotic events in prostate cancer cells. Additionally, some studies have found that high expression of STEAP2 is associated with prolonged survival in patients with glioblastoma multiforme (GBM), where most immune processes are more active in high-risk glioma groups, resulting in a richer presence of immune cells such as M0 macrophages, M1 macrophages, M2 macrophages, and neutrophils. Furthermore, research has indicated that STEAP2 is significantly upregulated at the base of colonic crypts in colon cancer, suggesting its involvement in the occurrence and progression of colorectal diseases.
Alternative Names
Anti-STAMP1 monoclonal antibody
Anti-six transmembrane protein of prostate 1 monoclonal antibody
References
- 1. Gomes IM, et al. STEAP proteins: from structure to applications in cancer therapy. Mol Cancer Res. 2012 May;10(5):573-87.
- 2. Rocha SM, et al. The Usefulness of STEAP Proteins in Prostate Cancer Clinical Practice. In: Bott SRJ, Ng KL, editors. Prostate Cancer [Internet]. Brisbane (AU): Exon Publications; 2021 May 27. Chapter 10.
References
Mechanistic analysis of iron accumulation by endothelial cells of the BBB
BIOMETALS
Authors: McCarthy, Ryan C.; Kosman, Daniel J.
Abstract
The mechanism(s) by which iron in blood is transported across the blood-brain barrier (BBB) remains controversial. Here we have examined the first step of this trans-cellular pathway, namely the mechanism(s) of iron uptake into human brain microvascular endothelial cells (hBMVEC). We show that hBMVEC actively reduce non-transferrin bound Fe-III (NTBI) and transferrin-bound Fe-III (TBI); this activity is associated with one or more ferrireductases. Efficient, exo-cytoplasmic ferri-reduction from TBI is dependent upon transferrin receptor (TfR), also. Blocking holo-Tf binding with an anti-TfR antibody significantly decreases the reduction of iron from transferrin by hBMVEC, suggesting that holo-Tf needs to bind to TfR in order for efficient reduction to occur. Ferri-reduction from TBI significantly decreases when hBMVEC are pre-treated with Pt-II, an inhibitor of cell surface reductase activity. Uptake of Fe-59 from Fe-59-Tf by endothelial cells is inhibited by 50 % when ferrozine is added to solution; in contrast, no inhibition occurs when cells are alkalinized with NH4Cl. This indicates that the iron reduced from holo-transferrin at the plasma membrane accounts for at least 50 % of the iron uptake observed. hBMVEC-dependent reduction and uptake of NTBI utilizes a Pt-II-insensitive reductase. Reductase-independent uptake of Fe-II by hBMVEC is inhibited up to 50 % by Zn-II and/or Mn-II by a saturable process suggesting that redundant Fe-II transporters exist in the hBMVEC plasma membrane. These results are the first to demonstrate multiple mechanism(s) of TBI and NTBI reduction and uptake by endothelial cells (EC) of the BBB.
Six-Transmembrane Epithelial Antigen of the Prostate (STEAP1 and STEAP2)-Differentially Expressed by Murine and Human Mesenchymal Stem Cells
TISSUE ENGINEERING PART A
Authors: Vaghjiani, Rasilaben J.; Talma, Sonia; Murphy, Christopher L.
Abstract
Mesenchymal stem cells (MSCs) have great potential for cell-based therapies. However, lack of cell-specific markers thwarts full realization of this as it prevents their identification in vivo, and subsequent purification. In the present study, to ensure cell purity multiple individual clones were derived from the bone marrow of BALB/b and BALB/c mice, and subsequently defined as MSCs by demonstrating their multipotentiality and self-renewal ability. In an effort to define the molecular signature of such MSCs and identify potentially cell-specific markers, an extensive genome-wide microarray analysis was performed comparing eight individual undifferentiated MSC clones to four different controls-corresponding differentiated MSC clones, bone marrow adherent cells, freshly isolated bone marrow cells, and embryonic fibroblasts. Strikingly, all MSC clones expressed differentially high levels of six-transmembrane epithelial antigen of the prostate (STEAP1 and STEAP2). Further, both STEAP members showed an extremely similar expression profile to stem cell antigen-1 (Sca-1) as demonstrated by two-dimensional hierarchical cluster analysis. Most importantly, differentially high levels of STEAP1 and STEAP2 proteins were also detected in human multipotent bone marrow adherent cultures. Thus, STEAPs may represent novel markers of MSCs in man as well as mice. Depletion of STEAP1 in human MSCs using RNAi resulted in decreased cell adhesion to tissue culture plastic. Further work is now needed to fully uncover its function in these cells, and to explore its potential as a marker of MSCs.
COA
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