Clinical significance of STEAP1 extracellular vesicles in prostate cancer

Khanna, Karan; Salmond, Nikki; Lynn, Kalan; Leong, Hon S.; Williams, Karla C.

doi:10.1038/s41391-021-00319-2

Cited by 24 publications

(26 citation statements)

References 49 publications

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“…One method of using STEAP1 as a biomarker is detecting the number of circulating STEAP1-positive extracellular vesicles (EVs). In two studies, PCa patients were found to have significantly elevated STEAP1 EV levels when compared to healthy males [ 55 , 56 ]. Khanna et al concluded that EV-based liquid biopsy may be a useful diagnostic strategy in PCa, but they found no association between total STEAP1 EV levels and disease recurrence or overall survival [ 55 ].…”

Section: Steap1–4 As Biomarkers and Therapeutic Targets For Prostate ...mentioning

confidence: 99%

STEAP1–4 (Six-Transmembrane Epithelial Antigen of the Prostate 1–4) and Their Clinical Implications for Prostate Cancer

Evans

Bizzaro

et al. 2022

Cancers

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Six-Transmembrane Epithelial Antigen of the Prostate 1–4 (STEAP1–4) compose a family of metalloproteinases involved in iron and copper homeostasis and other cellular processes. Thus far, five homologs are known: STEAP1, STEAP1B, STEAP2, STEAP3, and STEAP4. In prostate cancer, STEAP1, STEAP2, and STEAP4 are overexpressed, while STEAP3 expression is downregulated. Although the metalloreductase activities of STEAP1–4 are well documented, their other biological functions are not. Furthermore, the properties and expression levels of STEAP heterotrimers, homotrimers, heterodimers, and homodimers are not well understood. Nevertheless, studies over the last few decades have provided sufficient impetus to investigate STEAP1–4 as potential biomarkers and therapeutic targets for prostate cancer. In particular, STEAP1 is the target of many emerging immunotherapies. Herein, we give an overview of the structure, physiology, and pathophysiology of STEAP1–4 to provide context for past and current efforts to translate STEAP1–4 into the clinic.

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Section: Steap1–4 As Biomarkers and Therapeutic Targets For Prostate ...mentioning

confidence: 99%

STEAP1–4 (Six-Transmembrane Epithelial Antigen of the Prostate 1–4) and Their Clinical Implications for Prostate Cancer

Evans

Bizzaro

et al. 2022

Cancers

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“…Investigating inferred genes for the Androgen Resonse factor, we discover several previously known biomarkers of clinical relevance such as STEAP1, SLC45A3 [Perner et al, 2013] and ACPP. The six-transmembrane epithelial antigen of the prostate 1 (STEAP1) is overexpressed in prostate cancer and serves as a diagnostic and prognostic biomarker [Khanna et al, 2021]. Also, it has been shown that levels of ACPP or prostatic specific acid phosphatase (PSAP), increase with prostate cancer progression [Kong and Byun, 2013].…”

Section: Thementioning

confidence: 99%

Encoding Domain Knowledge in Multi-view Latent Variable Models: A Bayesian Approach with Structured Sparsity

Qoku¹,

Buettner²

2022

Preprint

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Many real-world systems are described not only by data from a single source but via multiple data views. For example, in genomic medicine, a patient can be described by data from different molecular layers. This raises the need for multi-view models that are able to disentangle variation within and across data views in an interpretable manner. Latent variable models with structured sparsity are a commonly used tool to address this modeling task but interpretability is cumbersome since it requires a direct inspection and interpretation of each factor via a specialized domain expert. Here, we propose MuVI, a novel approach for domain-informed multi-view latent variable models, facilitating the analysis of multiview data in an inherently explainable manner. We demonstrate that our model (i) is able to integrate noisy domain expertise in form of feature sets, (ii) is robust to noise in the encoded domain knowledge, (iii) results in identifiable factors and (iv) is able to infer interpretable and biologically meaningful axes of variation in a real-world multiview dataset of cancer patients.

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“…If EwS EVs cause STEAP1 expression to activate STAT1 in recipient T cells, EVs may thus reverse the STAT1 downregulation exerted by T cells, hence reinforcing the antiproliferative effects induced by type I interferon potentially present in the TME (Gajewski et al, 2013). While STEAP1 expression in EwS cells is associated with poor outcome (Grunewald et al, 2012b), no association was found between the detection of STEAP1 in prostate cancer EVs and its clinical outcome (Khanna et al, 2021). Hence, the exact role of STEAP1 transcripts in EwS EVs requires further investigation.…”

Section: T Cellsmentioning

confidence: 99%

“…Therefore, research into this possibility is warranted. Recently, it was shown in prostate cancer that patients' plasma samples presented significantly higher STEAP1positive EVs compared to healthy individuals, as analyzed by nanoscale flow cytometry (Khanna et al, 2021). Therefore, presence of STEAP1 in EVs of EwS patients' samples as well as its association with clinical outcomes should be assessed.…”

Section: Clinical Applications Of Ewing Sarcoma Extracellular Vesiclesmentioning

confidence: 99%

Extracellular Vesicles in Reprogramming of the Ewing Sarcoma Tumor Microenvironment

Pachva

Lai

Jia

et al. 2021

Front. Cell Dev. Biol.

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Ewing sarcoma (EwS) is a highly aggressive cancer and the second most common malignant bone tumor of children and young adults. Although patients with localized disease have a survival rate of approximately 75%, the prognosis for patients with metastatic disease remains dismal (<30%) and has not improved in decades. Standard-of-care treatments include local therapies such as surgery and radiotherapy, in addition to poly-agent adjuvant chemotherapy, and are often associated with long-term disability and reduced quality of life. Novel targeted therapeutic strategies that are more efficacious and less toxic are therefore desperately needed, particularly for metastatic disease, given that the presence of metastasis remains the most powerful predictor of poor outcome in EwS. Intercellular communication within the tumor microenvironment is emerging as a crucial mechanism for cancer cells to establish immunosuppressive and cancer-permissive environments, potentially leading to metastasis. Altering this communication within the tumor microenvironment, thereby preventing the transfer of oncogenic signals and molecules, represents a highly promising therapeutic strategy. To achieve this, extracellular vesicles (EVs) offer a candidate mechanism as they are actively released by tumor cells and enriched with proteins and RNAs. EVs are membrane-bound particles released by normal and tumor cells, that play pivotal roles in intercellular communication, including cross-talk between tumor, stromal fibroblast, and immune cells in the local tumor microenvironment and systemic circulation. EwS EVs, including the smaller exosomes and larger microvesicles, have the potential to reprogram a diversity of cells in the tumor microenvironment, by transferring various biomolecules in a cell-specific manner. Insights into the various biomolecules packed in EwS EVs as cargos and the molecular changes they trigger in recipient cells of the tumor microenvironment will shed light on various potential targets for therapeutic intervention in EwS. This review details EwS EVs composition, their potential role in metastasis and in the reprogramming of various cells of the tumor microenvironment, and the potential for clinical intervention.

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Clinical significance of STEAP1 extracellular vesicles in prostate cancer

Cited by 24 publications

References 49 publications

STEAP1–4 (Six-Transmembrane Epithelial Antigen of the Prostate 1–4) and Their Clinical Implications for Prostate Cancer

STEAP1–4 (Six-Transmembrane Epithelial Antigen of the Prostate 1–4) and Their Clinical Implications for Prostate Cancer

Encoding Domain Knowledge in Multi-view Latent Variable Models: A Bayesian Approach with Structured Sparsity

Extracellular Vesicles in Reprogramming of the Ewing Sarcoma Tumor Microenvironment

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