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Nature Cancer May 2023Tumor expression of prostate-specific membrane antigen (PSMA) is lost in 15-20% of men with castration-resistant prostate cancer (CRPC), yet the underlying mechanisms...
Tumor expression of prostate-specific membrane antigen (PSMA) is lost in 15-20% of men with castration-resistant prostate cancer (CRPC), yet the underlying mechanisms remain poorly defined. In androgen receptor (AR)-positive CRPC, we observed lower PSMA expression in liver lesions versus other sites, suggesting a role of the microenvironment in modulating PSMA. PSMA suppression was associated with promoter histone 3 lysine 27 methylation and higher levels of neutral amino acid transporters, correlating with F-fluciclovine uptake on positron emission tomography imaging. While PSMA is regulated by AR, we identified a subset of AR-negative CRPC with high PSMA. HOXB13 and AR co-occupancy at the PSMA enhancer and knockout models point to HOXB13 as an upstream regulator of PSMA in AR-positive and AR-negative prostate cancer. These data demonstrate how PSMA expression is differentially regulated across metastatic lesions and in the context of the AR, which may inform selection for PSMA-targeted therapies and development of complementary biomarkers.
Topics: Male; Humans; Prostatic Neoplasms, Castration-Resistant; Prostate; Prostate-Specific Antigen; Positron-Emission Tomography; Tumor Microenvironment
PubMed: 37038004
DOI: 10.1038/s43018-023-00539-6 -
Australian Journal of General Practice Mar 2023
Topics: Male; Humans; Prostate-Specific Antigen; Decision Making, Shared
PubMed: 36872085
DOI: 10.31128/AJGP-01-23-6692 -
Urologie (Heidelberg, Germany) Apr 2023
Topics: Male; Humans; Prostatic Neoplasms; Prostate-Specific Antigen; Hormones
PubMed: 37014381
DOI: 10.1007/s00120-023-02054-z -
The Journal of Applied Laboratory... May 2023
Topics: Male; Female; Humans; Prostate-Specific Antigen; Breast Neoplasms; Biomarkers, Tumor
PubMed: 36760007
DOI: 10.1093/jalm/jfad002 -
BJU International Mar 2023
Topics: Male; Humans; Prostate-Specific Antigen; Prostatic Neoplasms; Early Detection of Cancer; Mass Screening
PubMed: 36808808
DOI: 10.1111/bju.15967 -
Archives of Pathology & Laboratory... Sep 2019
Topics: Factor V; Hepatitis A; Humans; Male; Prostate-Specific Antigen; Thrombophilia
PubMed: 31453732
DOI: 10.5858/arpa.2019-0222-LE -
Revista Da Associacao Medica Brasileira... 2023
Topics: Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Biomarkers, Tumor
PubMed: 36820778
DOI: 10.1590/1806-9282.20221590 -
Investigative and Clinical Urology Sep 2023
Topics: Male; Humans; Prostate-Specific Antigen; Early Detection of Cancer; Prostatic Neoplasms
PubMed: 37668197
DOI: 10.4111/icu.20230229 -
Tidsskrift For Den Norske Laegeforening... Sep 2023
Topics: Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 37668127
DOI: 10.4045/tidsskr.23.0530 -
Aktuelle Urologie Aug 2023
Topics: Male; Humans; Prostatic Neoplasms, Castration-Resistant; Prostate-Specific Antigen; Taxoids
PubMed: 37541233
DOI: 10.1055/a-2084-8214