Calcifications in prostate cancer: An active phenomenon mediated by epithelial cells with osteoblast‐phenotype

2018 ◽  
Vol 81 (7) ◽  
pp. 745-748 ◽  
Author(s):  
Manuel Scimeca ◽  
Rita Bonfiglio ◽  
Fabiana Varone ◽  
Sara Ciuffa ◽  
Alessandro Mauriello ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Epithelial Cells ◽  
Active Phenomenon

Localized activation of the metastatic phenotype within the perineural region in prostate cancer.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 253-253
Author(s):  
Mick D. Brown ◽  
Claire Alexandre Hart ◽  
Ashwin Sachdeva ◽  
Christian Faulkner ◽  
David Wedge ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Epithelial Cells ◽  
Pathological Finding ◽  
Clinical History ◽  
Metastatic Progression ◽  
Metastatic Phenotype ◽  
Increased Risk ◽  
Phenotypic Characterisation ◽  
Local Tumour ◽  
Tumour Lesion

253 Background: Perineural Invasion (PNI) is defined as malignant epithelial cell invasion of the perineural space and nerves. Despite widespread acknowledgement of the clinical significance of PNI as a PCa pathological finding associated with recurrence, increased risk of bone metastasis and poor survival, the molecular mechanism underlying this pathology is relatively unknown. The malignant epithelial cells within the PNI potentially provides a spatially defined “snapshot” of disease progression, as the cells switch to a more migrational phenotype associated with metastatic progression. Here we present the initial spatial PNI phenotypic characterisation in PCa. Methods: Archival FFPE blocks, with associated full clinical history, from patients who underwent a radical prostatectomy for prostate cancer were retrieved under research ethics REC#07/H1003/161+5 10_NOCL_02. Biomarkers EphA2, pEphA2s897, pMLC2, E-Cadherin, Vimentin, TOMM20, MTC01, NDUFB8, PTEN were assessed on 4µm serial sections stained using a multiplex TSA protocol, with S100, pan-cytokeratin and DAPI acting as landmarks, on a Ventana Discovery platform prior to scanning on a Versa 3 platform with Halo image analysis. Prostate zones were defined at 500µm intervals either side of the prostate capsule. Univariate and multivariate (hierarchical clustering, UMap clustering) expression analysis and correlation with clinic-pathological features was conducted within R. Results: The PNI epithelial cells within each spatial zone of the prostate are significantly different to each other (Kruskal-Wallis test p < 2.2x10−16 except for MTC01 p = 5.3x10−10). In comparison with the local tumour lesion, PNI epithelial cells localised within 1000µm of the prostate edge and outside the tumour lesion, have undergone a migrational switch, gaining features associated with an activated metastatic phenotype, with increased expression of amoeboid signalling (EphA2, pEphA2s897, pMLC2) and mitochondrial defects (loss of Complex I and IV, gain of mitochondrial mass (TOMM20)). Patients clustering by multivariate expression trends across the prostate regions showed 4 distinct patient groups, with PNI epithelial cells in patient group 1 & 2 displaying a more epithelial to mesenchymal (EMT) phenotype, especially in the first 1000µm inside the prostate organ. Conclusions: Cells within PNI close to the edge of the prostate have features consistent with a switch to migrational/metastatic activation in contrast to the more indolent cell type found deeper within the tumour. Further characterisation of this localised migrational upregulation will help in understanding the transition from a localised to a metastatic phenotype.

Differential expression of neutral endopeptidase-24.11 (neprilysin) and endothelin-converting enzyme in human prostate cancer cell lines

2002 ◽  
Vol 103 (s2002) ◽  
pp. 314S-317S ◽  
Author(s):  
Badar A. USMANI ◽  
Ben HARDEN ◽  
Norman J. MAITLAND ◽  
Anthony J. TURNER
Keyword(s):  
Prostate Cancer ◽  
Epithelial Cells ◽  
Cell Lines ◽  
Prostate Cancer Cell ◽  
Neutral Endopeptidase ◽  
Prostatic Hyperplasia ◽  
Converting Enzyme ◽  
Prostate Cancer Cell Lines ◽  
Endothelin Converting Enzyme ◽  
Androgen Independent

Neutral endopeptidase-24.11 (neprilysin; NEP/CD10) is a cell surface metallopeptidase expressed by prostatic epithelial cells that degrades various bioactive peptides including endothelin. Endothelin-converting enzyme (ECE), the key enzyme of endothelin biosynthesis, catalyses the final processing step in the pathway. Neuropeptide substrates of NEP, including endothelin, have been implicated in the growth of androgen-independent prostate cancer. We have surveyed the expression of NEP and ECE in a range of prostate cancer cell lines. Western analysis reveals that ECE-1 is expressed abundantly in all the malignant cell lines tested, except for LNCaP. In contrast, LNCaP cells express high levels of NEP, while NEP was not detected in PC-3, DU145 and other metastatic cell lines that were tested. Of the normal immortalized prostate epithelial cell lines, PNT1a shows equivalent amounts of NEP and ECE. PNT2-C2 shows poor NEP expression but an abundance of ECE. P4E6, by comparison, has low levels of both ECE and NEP. These differences in expression may render these cell lines useful in experimental models for future study. Benign prostatic hyperplasia primary epithelial cells express much higher levels of NEP than malignant primary epithelial cells, but neither show ECE expression. On the other hand, surrounding stromal cell populations have detectable ECE levels. An absence of ECE in malignant and benign prostatic hyperplasia cells of primary epithelial origin suggests an important role for stromal interaction and paracrine production of ECE within the host. The upregulation of ECE expression in metastatic cells in culture may be indicative of its role in metastatic progression. A differential profile of ECE and NEP could contribute to an abundance of mitogenic peptides aiding the progression of androgen-independent prostate cancer.

scholarly journals GPX1 Localizes to the Nucleus in Prostate Epithelium and its Levels are not Associated with Prostate Cancer Recurrence

Antioxidants ◽  
2018 ◽  
Vol 7 (11) ◽  
pp. 167 ◽  
Author(s):  
Dede Ekoue ◽  
Emmanuel Ansong ◽  
Lenny Hong ◽  
Larisa Nonn ◽  
Virgilia Macias ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Epithelial Cells ◽  
Prostate Cancer Risk ◽  
Cancer Recurrence ◽  
Lipid Peroxides ◽  
Cancer Tissue ◽  
Nuclear Staining ◽  
Dietary Intakes ◽  
Prostate Epithelial Cells ◽  
Prostate Cancer Recurrence

Glutathione peroxidase 1 (GPX1) is an extensively studied selenium-dependent protein that reduces hydrogen and lipid peroxides to water. Because of its antioxidant function and its responsiveness to dietary intakes of selenium, an essential trace element whose levels are inversely associated with prostate cancer risk, GPX1 levels were assessed in a prostate cancer tissue microarray, comparing cases of recurrent prostate cancer following prostatectomy to non-recurrent controls. While GPX1 is generally considered as a protein that resides in both the cytoplasm and mitochondria, we detected strong nuclear staining by immunofluorescence using GPX1-specific antibodies. Nuclear localization of GPX1 was also observed in both primary prostate epithelial cells and the immortalized prostate-derived cell line RWPE-1, but not in LNCaP or PC3 prostate tumor-derived cell lines. Quantification of GPX1 levels in the entire cell, the cytoplasm, and the nucleus did not indicate any association of either its levels or subcellular distribution with prostate cancer recurrence. While GPX1 levels may not have an impact on survival among men with prostate cancer, the data indicates that this extensively characterized protein may have a novel function in the nucleus of prostate epithelial cells.

scholarly journals Bacterial Lipopolysaccharide Augmented Malignant Transformation and Promoted the Stemness in Prostate Cancer Epithelial Cells

2021 ◽  
Vol Volume 14 ◽  
pp. 5849-5862
Author(s):  
Sijie Tang ◽  
Xueqi Lian ◽  
Huiying Cheng ◽  
Jiaqian Guo ◽  
Daguang Ni ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Epithelial Cells ◽  
Malignant Transformation ◽  
Bacterial Lipopolysaccharide

Basal prostate epithelial cells stimulate the migration of prostate cancer cells

2004 ◽  
Vol 41 (2) ◽  
pp. 85-97 ◽  
Author(s):  
Hsiao-Man Yu ◽  
Diane E. Frank ◽  
Jie Zhang ◽  
Xueke You ◽  
William G. Carter ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Epithelial Cells ◽  
Cancer Cells ◽  
Prostate Cancer Cells ◽  
Prostate Epithelial Cells

scholarly journals Proteolytic cleavage and truncation of NDRG1 in human prostate cancer cells, but not normal prostate epithelial cells

2013 ◽  
Vol 33 (3) ◽  
Author(s):  
Mohammad K. Ghalayini ◽  
Qihan Dong ◽  
Des R. Richardson ◽  
Stephen J. Assinder
Keyword(s):  
Prostate Cancer ◽  
Epithelial Cells ◽  
Western Blot ◽  
Cancer Cells ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Metastasis Suppressor ◽  
Normal Prostate ◽  
Truncated Protein ◽  
Prostate Epithelial Cells

NDRG1 (N-myc downstream regulated gene-1) is a metastasis suppressor that is down-regulated in prostate cancer. NDRG1 phosphorylation is associated with inhibition of metastasis and Western blots indicate two bands at ~41 and ~46 kDa. Previous investigations by others suggest the higher band is due to NDRG1 phosphorylation. However, the current study using a dephosphorylation assay and the Phos-tag (phosphate-binding tag) SDS/PAGE assay, demonstrated that the 46 kDa NDRG1 protein band was not due to phosphorylation. Further experiments showed that the NDRG1 protein bands were not affected upon glycosidase treatment, despite marked effects of these enzymes on the glycosylated protein, fetuin. Analysis using RT–PCR (reverse transcriptase–PCR) demonstrated only a single amplicon, and thus, the two bands could not result from an alternatively spliced NDRG1 transcript. Western-blot analysis of prostate cancer cell lysates identified the 41 kDa band to be a truncated form of NDRG1, with MS confirming the full and truncated proteins to be NDRG1. Significantly, this truncated protein was not present in normal human PrECs (prostate epithelial cells). Western-blot analysis using anti-NDRG1 raised to its N-terminal sequence failed to detect the truncated protein, suggesting that it lacked N-terminus amino acids (residues 1–49). Sequence analysis predicted a pseudotrypsin protease cleavage site between Cys49–Gly50. Such cleavage of NDRG1 in cancer cells may result in loss of NDRG1 tumour suppressive activity.

scholarly journals Primary cell cultures as models of prostate cancer development

2005 ◽  
Vol 12 (1) ◽  
pp. 19-47 ◽  
Author(s):  
D M Peehl
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Epithelial Cells ◽  
Cancer Progression ◽  
Biological Activities ◽  
Primary Cultures ◽  
Neuroendocrine Cells ◽  
Biological Behavior ◽  
Full Potential ◽  
Cell Surface Antigens

This review focuses on primary cultures of human prostatic epithelial cells and their applications as models of normal and malignant biological behavior. Current abilities to culture cells from normal tissues, from premalignant dysplastic lesions (prostatic intraepithelial neoplasia), from primary adenocarcinomas, and from metastases are described. Evidence for representation of the interrelated cells of the normal prostatic epithelium — stem cells, basal epithelial cells, secretory epithelial cells, transit amplifying cells and neuroendocrine cells — in primary cultures is presented. Comparisons between normal and cancer-derived primary cultures are made regarding biological activities relevant to carcinogenesis, such as proliferation, apoptosis, differentiation, senescence, adhesion, migration, invasion, steroid hormone metabolism, other metabolic pathways and angiogenesis. Analyses of tumor suppressor activity, differential gene expression and cytogenetics in primary cultures have revealed changes relevant to prostate cancer progression. Preclinical studies with primary cultures have provided information useful for designing new strategies for chemoprevention, chemotherapy, cytotoxin therapy, radiation therapy, gene therapy and imaging. While the behavior of normal primary cultures is often used as a basis for comparison with established, immortal prostate cancer cell lines, the most informative studies are performed with donor-matched pairs of normal and malignant primary cultures, grown under identical conditions. Challenges that remain to be addressed if the full potential of primary cultures as a model system is to be realized include isolation, culture and characterization of stem cells, improved methodology to induce or maintain a fully differentiated, androgen-responsive phenotype, and identification of cell surface antigens or other markers with which to purify pure populations of live cancer or premalignant cells apart from non-malignant epithelial cells prior to culture.

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