scholarly journals Prostate Osteoblast-Like Cells: A Reliable Prognostic Marker of Bone Metastasis in Prostate Cancer Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Manuel Scimeca ◽  
Nicoletta Urbano ◽  
Bonfiglio Rita ◽  
Sarah Natalia Mapelli ◽  
Carlo Vittorio Catapano ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Clinical Evidence ◽  
Prostate Cancer Cells ◽  
Ultrastructural Studies ◽  
Pet Ct ◽  
Ct Analysis ◽  
Malignant Lesions

The main aim of this study was to investigate the putative association among the presence of prostate cancer cells, defined as prostate osteoblast-like cells (POLCs), and showing the expression of typical morphological and molecular characteristics of osteoblasts, the development of bone metastasis within 5 years of diagnosis, and the uptake of 18F-choline evaluated by PET/CT analysis. To this end, prostate biopsies (n= 110) were collected comprising 44 benign lesions and 66 malignant lesions. Malignant lesions were further subdivided into two groups: biopsies from patients that had clinical evidence of bone metastasis (BM+,n= 23) and biopsies from patients that did not have clinical evidence of bone metastasis within 5 years (BM−,n= 43). Paraffin serial sections were obtained from each specimen to perform histological classifications and immunohistochemical (IHC) analysis. Small fragments of tissue were used to perform ultrastructural and microanalytical investigations. IHC demonstrated the expression of markers of epithelial-to-mesenchymal transition (VIM), bone mineralization, and osteoblastic differentiation (BMP-2, PTX-3, RUNX2, RANKL, and VDR) in prostate lesions characterized by the presence of calcium-phosphate microcalcifications and high metastatic potential. Ultrastructural studies revealed the presence of prostate cancer cells with osteoblast phenotype close to microcalcifications. Noteworthy, PET/CT analysis showed higher uptake of 18F-choline in BM+ lesions with high positivity (≥300/500 cells) for RUNX2 and/or RANKL immunostaining. Although these data require further investigations about the molecular mechanisms of POLCs generation and role in bone metastasis, our study can open new and interesting prospective in the management of prostate cancer patients. The presence of POLCs along with prostate microcalcifications may become negative prognostic markers of the occurrence of bone metastases.

scholarly journals Tumor- and osteoclast-derived NRP2 in prostate cancer bone metastases

Bone Research ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Navatha Shree Polavaram ◽  
Samikshan Dutta ◽  
Ridwan Islam ◽  
Arup K. Bag ◽  
Sohini Roy ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Osteoclast Differentiation ◽  
Potential Effect ◽  
Tumor Burden ◽  
Bone Lesions ◽  
Prostate Cancer Cells

AbstractUnderstanding the role of neuropilin 2 (NRP2) in prostate cancer cells as well as in the bone microenvironment is pivotal in the development of an effective targeted therapy for the treatment of prostate cancer bone metastasis. We observed a significant upregulation of NRP2 in prostate cancer cells metastasized to bone. Here, we report that targeting NRP2 in cancer cells can enhance taxane-based chemotherapy with a better therapeutic outcome in bone metastasis, implicating NRP2 as a promising therapeutic target. Since, osteoclasts present in the tumor microenvironment express NRP2, we have investigated the potential effect of targeting NRP2 in osteoclasts. Our results revealed NRP2 negatively regulates osteoclast differentiation and function in the presence of prostate cancer cells that promotes mixed bone lesions. Our study further delineated the molecular mechanisms by which NRP2 regulates osteoclast function. Interestingly, depletion of NRP2 in osteoclasts in vivo showed a decrease in the overall prostate tumor burden in the bone. These results therefore indicate that targeting NRP2 in prostate cancer cells as well as in the osteoclastic compartment can be beneficial in the treatment of prostate cancer bone metastasis.

scholarly journals Runx2 transcriptome of prostate cancer cells: insights into invasiveness and bone metastasis

2010 ◽  
Vol 9 (1) ◽  
pp. 258 ◽  
Author(s):  
Sanjeev K Baniwal ◽  
Omar Khalid ◽  
Yankel Gabet ◽  
Ruchir R Shah ◽  
Daniel J Purcell ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Cancer Cells ◽  
Prostate Cancer Cells

scholarly journals Total-Body 68Ga-PSMA-11 PET/CT for Bone Metastasis Detection in Prostate Cancer Patients: Potential Impact on Bone Scan Guidelines

2019 ◽  
Vol 61 (3) ◽  
pp. 405-411 ◽  
Author(s):  
Kelsey L. Pomykala ◽  
Johannes Czernin ◽  
Tristan R. Grogan ◽  
Wesley R. Armstrong ◽  
John Williams ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Cancer Patients ◽  
Bone Scan ◽  
Pet Ct ◽  
Potential Impact ◽  
Total Body

scholarly journals Glycidamide Promotes the Growth and Migratory Ability of Prostate Cancer Cells by Changing the Protein Expression of Cell Cycle Regulators and Epithelial-to-Mesenchymal Transition (EMT)-Associated Proteins with Prognostic Relevance

2019 ◽  
Vol 20 (9) ◽  
pp. 2199
Author(s):  
Titus Ime Ekanem ◽  
Chi-Chen Huang ◽  
Ming-Heng Wu ◽  
Ding-Yen Lin ◽  
Wen-Fu T. Lai ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Protein Expression ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Epithelial To Mesenchymal Transition ◽  
Gene Signature ◽  
Prostate Cancer Cells ◽  
Mesenchymal Transition ◽  
Prognostic Relevance

Acrylamide (AA) and glycidamide (GA) can be produced in carbohydrate-rich food when heated at a high temperature, which can induce a malignant transformation. It has been demonstrated that GA is more mutagenic than AA. It has been shown that the proliferation rate of some cancer cells are increased by treatment with GA; however, the exact genes that are induced by GA in most cancer cells are not clear. In the present study, we demonstrated that GA promotes the growth of prostate cancer cells through induced protein expression of the cell cycle regulator. In addition, we also found that GA promoted the migratory ability of prostate cancer cells through induced epithelial-to-mesenchymal transition (EMT)-associated protein expression. In order to understand the potential prognostic relevance of GA-mediated regulators of the cell cycle and EMT, we present a three-gene signature to evaluate the prognosis of prostate cancer patients. Further investigations suggested that the three-gene signature (CDK4, TWIST1 and SNAI2) predicted the chances of survival better than any of the three genes alone for the first time. In conclusion, we suggested that the three-gene signature model can act as marker of GA exposure. Hence, this multi-gene panel may serve as a promising outcome predictor and potential therapeutic target in prostate cancer patients.

scholarly journals Androgen Receptor Signaling Regulates the Transcriptome of Prostate Cancer Cells by Modulating Global Alternative Splicing

2019 ◽  
Author(s):  
Kalpit Shah ◽  
Teresa Gagliano ◽  
Lisa Garland ◽  
Timothy O’Hanlon ◽  
Daria Bortolotti ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Alternative Splicing ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Treatment Resistance ◽  
Progression Free Survival ◽  
Therapeutic Interventions ◽  
Prostate Cancer Cells

AbstractAndrogen receptor (AR), is a transcription factor and a member of a hormone receptor superfamily. AR plays a vital role in the progression of prostate cancer and is a crucial target for therapeutic interventions. While the majority of advanced-stage prostate cancer patients will initially respond to the androgen-deprivation, the disease often progresses to castrate-resistant prostate cancer (CRPC). Interestingly, CRPC tumors continue to depend on hyperactive AR signaling and will respond to potent second-line anti-androgen therapies, including bicalutamide (CASODEX®) and enzalutamide (XTANDI®). However, the progression-free survival rate for the CRPC patients on anti-androgen therapies is only 8 to 19 months. Hence, there is a need to understand the mechanisms underlying CRPC progression and eventual treatment resistance. Here, we have leveraged next-generation sequencing and newly developed analytical methodologies to evaluate the role of AR-signaling in regulating the transcriptome of prostate cancer cells. The genomic and pharmacologic stimulation- and inhibition-of AR activity demonstrates that AR regulates alternative splicing within cancer-relevant genes. Furthermore, by integrating transcriptomic data from in vitro experiments and in prostate cancer patients, we found that a significant number of AR-regulated splicing events are associated with tumor progression. For example, we found evidence for an inadvertent AR-antagonist mediated switch in IDH1 and PL2G2A isoform expression, which is associated with a decrease in overall survival of patients. Mechanistically, we discovered that the epithelial-specific splicing regulators (ESRP1 and ESRP2), flank many AR-regulated alternatively spliced exons. And, using 2D-invasion assays, we show that the inhibition of ESRPs can suppress AR-antagonist driven tumor invasion. In conclusion, until now, AR signaling has been primarily thought to modulate transcriptome of prostate epithelial cells by inducing or suppressing gene expression. Our work provides evidence for a new mechanism by which AR alters the transcriptome of prostate cancer cells by modulating alternative splicing. As such, our work has important implications for CRPC progression and development of resistance to treatment with bicalutamide and enzalutamide.

scholarly journals Comparison of PET/CT and MRI in the Diagnosis of Bone Metastasis in Prostate Cancer Patients: A Network Analysis of Diagnostic Studies

2021 ◽  
Vol 11 ◽  
Author(s):  
Fanxiao Liu ◽  
Jinlei Dong ◽  
Yelong Shen ◽  
Canhua Yun ◽  
Ruixiao Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Diagnostic Value ◽  
High Quality ◽  
Psma Pet ◽  
Pet Ct ◽  
3.0 T ◽  
Diagnosis Of Bone Metastasis

BackgroundAccurate diagnosis of bone metastasis status of prostate cancer (PCa) is becoming increasingly more important in guiding local and systemic treatment. Positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) have increasingly been utilized globally to assess the bone metastases in PCa. Our meta-analysis was a high-volume series in which the utility of PET/CT with different radioligands was compared to MRI with different parameters in this setting.Materials and MethodsThree databases, including Medline, Embase, and Cochrane Library, were searched to retrieve original trials from their inception to August 31, 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. The methodological quality of the included studies was assessed by two independent investigators utilizing Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). A Bayesian network meta-analysis was performed using an arm-based model. Absolute sensitivity and specificity, relative sensitivity and specificity, diagnostic odds ratio (DOR), and superiority index, and their associated 95% confidence intervals (CI) were used to assess the diagnostic value.ResultsForty-five studies with 2,843 patients and 4,263 lesions were identified. Network meta-analysis reveals that 68Ga-labeled prostate membrane antigen (68Ga-PSMA) PET/CT has the highest superiority index (7.30) with the sensitivity of 0.91 and specificity of 0.99, followed by 18F-NaF, 11C-choline, 18F-choline, 18F-fludeoxyglucose (FDG), and 18F-fluciclovine PET/CT. The use of high magnetic field strength, multisequence, diffusion-weighted imaging (DWI), and more imaging planes will increase the diagnostic value of MRI for the detection of bone metastasis in prostate cancer patients. Where available, 3.0-T high-quality MRI approaches 68Ga-PSMA PET/CT was performed in the detection of bone metastasis on patient-based level (sensitivity, 0.94 vs. 0.91; specificity, 0.94 vs. 0.96; superiority index, 4.43 vs. 4.56).Conclusions68Ga-PSMA PET/CT is recommended for the diagnosis of bone metastasis in prostate cancer patients. Where available, 3.0-T high-quality MRI approaches 68Ga-PSMA PET/CT should be performed in the detection of bone metastasis.

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