Six-Transmembrane Epithelial Antigen of the Prostate (STEAP1 and STEAP2)—Differentially Expressed by Murine and Human Mesenchymal Stem Cells

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.

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“…There was no significant change in STAMP1 or STAMP3 expression, which differ from previous findings in murine cells [20,48,49]. In contrast, STEAP1 and STAMP2 levels increased throughout the adipogenesis process.…”

STEAP1 Is Associated with the Invasive and Oxidative Stress Phenotype of Ewing Tumors

“…Recently, STEAP1 was validated as a bona fide marker for mesenchymal stem cells (MSC; ref. 8) supporting the relationship of Ewing tumors with MSCs (9). Moreover, STEAP1 mRNA circulates in peripheral blood (6,10), and its detection in bone marrow of patients with Ewing tumors is indicative for occult Ewing tumor cells (11).…”

Fibroblast Growth Factor-2 Enhances Proliferation and Delays Loss of Chondrogenic Potential in Human Adult Bone-Marrow-Derived Mesenchymal Stem Cells

“…[51][52][53] Additionally, a recent report indicates that six transmembrane epithelial antigen of the prostate 1, also upregulated in cells with chondrogenic potential, may be a marker for MSCs. 54 Our data here must now be validated at the level of protein expression and signaling pathway activation to verify whether the different gene expression profiles detected translate into functional differences.…”