Background: Stem cells are postulated to mediate prostate cancer progression, and represent a small fraction of the entire tumor. Various proteins (α2-integrin, α6-integrin, CD117, CD133, EZH2, OCT3/4) are associated with a prostate cancer stem cell phenotype in cell lines and xenografts. Our objective was to investigate expression of stem cell markers in clinical prostate cancer in relation to outcome.
Methods: We validated immunohistochemical expression of stem cell markers in 481 prostate cancer patients and correlated expression with clinicopathologic parameters.
Results: Sporadic expression of α2-integrin was present in a fraction of tumor cells (<5%) in 94.7% of tumors and associated with PSA > 10 ng/ml (P = 0.04). α6-Integrin expression (<5%) occurred in 28.4% patients, while ≥5% α6-integrin expression was associated with PSA≤10 ng/ml (P = 0.01), Gleason score <7 (P < 0.01) and pT2-disease (P = 0.02). α6-integrin was predictive for biochemical recurrence (P < 0.01), local recurrence (P = 0.03) and disease specific death (P = 0.03). EZH2 expression was generally low with 2.6% of tumors showing ≥1% positive cells. EZH2 was associated with Gleason score ≥7 (P = 0.01) and biochemical recurrence (P = 0.01). We did not identify expression of CD117, CD133, and OCT3/4 in prostate cancer samples.
Conclusions: Expression of α2-integrin and EZH2 in a small fraction of prostate cancer cells is supportive for their role as stem cell marker. Although α6-integrin was not a unique stem cell marker, it was predictive for prostate cancer biochemical and local recurrence, and disease specific death. The validity of CD117, CD133, and OCT3/4 as prostate cancer stem cell marker is questionable since these proteins were not expressed in clinical prostate cancer.
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http://dx.doi.org/10.1002/pros.22768 | DOI Listing |
Eur J Nucl Med Mol Imaging
January 2025
Department of Nuclear Medicine, Affiliated Hospital of Jiangnan University, No. 1000, Hefeng Road, Wuxi, Jiangsu Province, 214000, China.
Purpose: A novel theranostic radiopharmaceutical targeting prostate-specific membrane antigen (PSMA), [Ga]Ga/[Lu]Lu-NYM032, was developed and its diagnostic and therapeutic potential in the treatment of prostate cancer (PCa) was preliminarily evaluated.
Methods: The diagnostic efficacy of the PET tracer [Ga]Ga-NYM032 was first evaluated in PSMA-positive xenograft-bearing models (LNCaP models), followed by evaluation in 10 PCa patients using [Ga]Ga-PSMA617 a comparator. Finally, the therapeutic potential of [Lu]Lu-NYM032 was evaluated in LNCaP models.
Endocr Connect
January 2025
Y Giwercman, Translational Medicine, Lund University, Malmö, Sweden.
Background: Prostate cancer therapy with surgical or chemical castration with GnRH agonists has been linked to elevated FSH levels, which may contribute to secondary health disorders, including atherosclerosis and diabetes. Although recent findings suggest a role for FSH beyond the reproductive system, its metabolic impact remains unclear and difficult to disentangle from that of androgens. In this study, we examined the metabolic changes induced by FSH and distinguished them from those caused by testosterone.
View Article and Find Full Text PDFClin Cancer Res
January 2025
University of Minnesota, Minneapolis, United States.
Purpose: 10-15% of prostate cancers (PCa) harbor recurrent FOXA1 aberrations whereby the alteration type and the effect on the forkhead( FKH) domain impacts protein-function. We developed a FOXA1 classification system to inform clinical management.
Experimental Design: 5,014 PCa were examined using whole exome and transcriptome sequencing from the Caris database.
Dis Model Mech
January 2025
Laboratory Genes and Disease, Department of Laboratory Medicine, Medical University of Vienna (MUW), Vienna, Austria.
Genetically engineered mouse models (GEMMs) are instrumental for modelling local and systemic features of complex diseases such as cancer. Non-invasive, longitudinal cell detection and monitoring in tumors, metastases and/or the micro-environment is paramount to achieve a better spatiotemporal understanding of cancer progression and to evaluate therapies in preclinical studies. Bioluminescent and fluorescent reporters marking tumor cells or their microenvironment are valuable for non-invasive cell detection and monitoring in vivo.
View Article and Find Full Text PDFAm J Mens Health
January 2025
Department of Emergency Ward, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
This study aims to investigate the effect and mechanism of cyclosporine A (CsA) on paclitaxel-resistant prostate cancer cells. Paclitaxel-resistant prostate cancer cell lines were established by gradual increment method. The proliferation of cells was tested using MTT and colony formation assay.
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