STEAP: A prostate-specific cell-surface antigen highly expressed in human prostate tumors

Hubert, René; Vivanco, Igor; Chen, Emily; Rastegar, Shiva; Leong, K.M.K.H.; Mitchell, S.C.; Madraswala, Rashida; Zhou, Yanhong; Kuo, James; Raitano, Arthur; Jakobovits, Aya; Saffran, Douglas C.; Afar, Daniel

doi:10.1073/pnas.96.25.14523

Cited by 293 publications

(344 citation statements)

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“…(26) STEAP lacks the N-terminal half present in the STAMPs and is therefore likely to have a different function compared with other members of the family. (27) STAMP1 is highly restricted to prostate for expression and is overexpressed in prostate cancer compared with benign prostate tissue. (28,29) STAMP1 expression is correlated with the presence of functional AR, even though it appears not to be androgen regulated.…”

Section: Stamp Familymentioning

confidence: 99%

Androgen signaling and its interactions with other signaling pathways in prostate cancer

2007

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SummaryProstate cancer is the most frequently diagnosed nonskin cancer and the third leading cause of cancer mortality in men. In the initial stages, prostate cancer is dependent on androgens for growth, which is the basis for androgen ablation therapy. However, in most cases, prostate cancer progresses to a hormone refractory phenotype for which there is no effective therapy available at present. The androgen receptor (AR) is required for prostate cancer growth in all stages, including the relapsed, ''androgen-independent'' tumors in the presence of very low levels of androgens. This review focuses on AR function and AR-target genes and summarizes the major signaling pathways implicated in prostate cancer progression, their crosstalk with each other and with AR signaling. This complex network of interactions is providing a deeper insight into prostate carcinogenesis and may form the basis for novel diagnostic and therapeutic strategies. IntroductionProstate adenocarcinoma is the most frequently diagnosed non-cutaneous male malignancy and the third leading cause of cancer-related death in men in most western industrialized countries. (1) It is estimated that around 660,000 men worldwide will be diagnosed with prostate cancer and 250,000 men will die from it in 2010; thus, it will remain a major health problem in the future. (1) It was more than 60 years ago that the important role of male sex hormones (androgens) for the development and growth of prostate cancer was demonstrated. (2) Accordingly, androgen ablation therapy has been the main line of therapy for prostate cancer. Therefore, much of the focus in prostate cancer research to date has naturally been on androgens, how to decrease the androgens in the circulation and how to inhibit the androgen receptor (AR).In addition to AR signaling, it has now become evident that other signaling pathways, as well as non-genomic and genomic alterations, are involved in prostate cancer development and progression. Furthermore, recent studies indicated that signaling through AR has a critical role even after androgen ablation and disease progression (for review see Ref.3). In the following sections, we give an overview of androgen signaling in prostate cancer, with a special focus on recent findings about AR function and AR target genes. We then review the involvement of other central signaling pathways in prostate cancer, with a special focus on their cross-talk with the AR signaling pathway. Clinical implications of these findings and potential directions for future research are also outlined.

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Section: Stamp Familymentioning

confidence: 99%

Androgen signaling and its interactions with other signaling pathways in prostate cancer

2007

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“…In contrast, STEAP1 mRNA is not detectable in blood of healthy donors and is hardly expressed in benign tissues, except for low amounts in urothelium and prostate (6,10). Because of its high tumor specificity and membrane-bound localization, STEAP1 might serve as a promising candidate for targeted therapy (6,10,11).…”

Section: Introductionmentioning

confidence: 97%

“…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).…”

Section: Introductionmentioning

confidence: 99%

“…Among STEAP proteins, only STEAP1 is overexpressed in many carcinomas including prostate and bladder cancer, where it locates to plasma and endosomal membranes (6,7), but its precise cellular function remains elusive. Recently, STEAP1 was validated as a bona fide marker for mesenchymal stem cells (MSC; ref.…”

Section: Introductionmentioning

confidence: 99%

“…Part of this signature is the six-transmembrane epithelial antigen of the prostate 1 (STEAP1)-a membrane-bound protein possibly contributing to transmembrane electron transfer (5,6).…”

Section: Introductionmentioning

confidence: 99%

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

Grünewald

Diebold

Espósito

et al. 2012

Molecular Cancer Research

114

132

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Ewing tumors comprise the second most common type of bone-associated cancer in children and are characterized by oncogenic EWS/FLI1 fusion proteins and early metastasis. Compelling evidence suggests that elevated levels of intracellular oxidative stress contribute to enhanced aggressiveness of numerous cancers, possibly including Ewing tumors. Using comprehensive microarray analyses and RNA interference, we identified the six-transmembrane epithelial antigen of the prostate 1 (STEAP1)-a membrane-bound mesenchymal stem cell marker of unknown function-as a highly expressed protein in Ewing tumors compared with benign tissues and show its regulation by EWS/FLI1. In addition, we show that STEAP1 knockdown reduces Ewing tumor proliferation, anchorage-independent colony formation as well as invasion in vitro and decreases growth and metastasis of Ewing tumor xenografts in vivo. Moreover, transcriptome and proteome analyses as well as functional studies revealed that STEAP1 expression correlates with oxidative stress responses and elevated levels of reactive oxygen species that in turn are able to regulate redox-sensitive and proinvasive genes. In synopsis, our data suggest that STEAP1 is associated with the invasive behavior and oxidative stress phenotype of Ewing tumors and point to a hitherto unanticipated oncogenic function of STEAP1. Mol Cancer Res; 10(1); 52-65. Ó2011 AACR.

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The T‐Body Approach: Towards Cancer Immuno‐Gene Therapy

Pinthus¹,

Eshhar

2002

Cancer Immune Therapy

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The T-body approach employs T cells redirected with antibody specificity using chimeric receptors (CRs). In this chapter we use the term T-bodies to define T cells bearing surface CRs. In functional terms, the CR combines antibody specificity in the form of Fv (variable region fragment) linked to a T cell stimulatory molecule. Primarily, we developed the T-body approach in order to endow T cells with predefined antibody specificity in order to study some physicochemical parameters involved in T cell activation (for review, see [1]). In the first design of the CR, we took advantage of the similarity in structure and genetic organization between the T cell receptor (TCR) and the antibody molecules, and replaced the variable (V) region of the TCR a and b chains with the antibody V H and V L [2]. Using the V region of antihapten antibodies we demonstrated that T cell hybridoma expressing such chimeric TCR genes could recognize antigen in an MHC-unrestricted manner, and could undergo activation for IL-2 production and target cell killing in a non-MHC-dependent manner [1].Quite readily,we and others have appreciated that T-bodies with antitumor specificity hold promise for cancer immunotherapy (for reviews, see [3,4]). The idea behind this assumption was to combine the availability of monoclonal antibodies (mAbs) towards tumor-associated antigens with the efficacy of tumor penetration and rejection of T cells. Using this combination we expected to overcome the inefficiency of antibodies in rejecting solid tumors, on the one hand, and difficulties in obtaining tumor-specific T cells, on the other.

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STEAP: A prostate-specific cell-surface antigen highly expressed in human prostate tumors

Cited by 293 publications

References 32 publications

Androgen signaling and its interactions with other signaling pathways in prostate cancer

Androgen signaling and its interactions with other signaling pathways in prostate cancer

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

The T‐Body Approach: Towards Cancer Immuno‐Gene Therapy

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