scholarly journals Prostate Cancer and Bone: The Elective Affinities

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Nadia Rucci ◽  
Adriano Angelucci
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Bone Microenvironment ◽  
Prostate Cancer Cells ◽  
Common Site ◽  
Osteolytic Lesions ◽  
Molecular Events ◽  
Elective Affinities ◽  
Molecular Affinity

The onset of metastases dramatically changes the prognosis of prostate cancer patients, determining increased morbidity and a drastic fall in survival expectancy. Bone is a common site of metastases in few types of cancer, and it represents the most frequent metastatic site in prostate cancer. Of note, the prevalence of tumor relapse to the bone appears to be increasing over the years, likely due to a longer overall survival of prostate cancer patients. Bone tropism represents an intriguing challenge for researchers also because the preference of prostate cancer cells for the bone is the result of a sequential series of targetable molecular events. Many factors have been associated with the peculiar ability of prostate cancer cells to migrate in bone marrow and to determine mixed osteoblastic/osteolytic lesions. As anticipated by the success of current targeted therapy aimed to block bone resorption, a better understanding of molecular affinity between prostate cancer and bone microenvironment will permit us to cure bone metastasis and to improve prognosis of prostate cancer patients.

Cathepsin K in the bone microenvironment: link between obesity and prostate cancer?

2007 ◽  
Vol 35 (4) ◽  
pp. 701-703 ◽  
Author(s):  
I. Podgorski ◽  
B.E. Linebaugh ◽  
B.F. Sloane
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Advanced Prostate Cancer ◽  
Bone Matrix ◽  
Cathepsin K ◽  
Collagen I ◽  
Skeletal Metastases ◽  
Bone Microenvironment ◽  
Prostate Cancer Cells ◽  
Common Site

The skeleton is the most common site of metastasis in patients with advanced prostate cancer. Despite many advances in targeting skeletal metastases, the mechanisms behind the attraction of prostate cancer cells to the bone are not known. Osteoclast cathepsin K, due to its ability to effectively degrade bone matrix collagen I, has been implicated in colonization and growth of prostate tumours in the bone. Identification of new cathepsin K substrates in the bone microenvironment and the recent findings demonstrating its involvement in obesity and inflammation suggest additional roles for this enzyme in skeletal metastases of prostate cancer.

An in vitro model of prostate cancer bone metastasis for highly metastatic and non-metastatic prostate cancer using nanoclay bone-mimetic scaffolds

MRS Advances ◽  
2019 ◽  
Vol 4 (21) ◽  
pp. 1207-1213 ◽  
Author(s):  
MD Shahjahan Molla ◽  
Dinesh R. Katti ◽  
Kalpana S. Katti
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Metastatic Prostate Cancer ◽  
Cancer Metastasis ◽  
Human Mesenchymal Stem Cells ◽  
Culture Technique ◽  
Complex Nature ◽  
Bone Microenvironment ◽  
Prostate Cancer Cells

ABSTRACTProstate cancer has a strong preference for metastasizing to bone which is the primary cause of prostate cancer-related morbidity and mortality. The complex nature of cancer metastasis requires the development of translational models that recapitulate a specific metastatic stage. Herein, we report the mimicking of mesenchymal to epithelial transition (MET) of prostate cancer cells using highly metastatic and a non-metastatic prostate cancer cell lines. A unique cell culture technique that we termed as ‘sequential culture’ was used to create a biomimetic bone microenvironment for metastasized prostate cancer cells by introducing bioactive factors from osteogenic induction of human mesenchymal stem cells (MSCs) within the porous 3D scaffolds. The in vitro 3D tumor model can be used as a testbed to study the interaction between prostate cancer and bone microenvironment and for the design of novel therapeutic studies.

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 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.

Bone microenvironment-related growth factors modulate differentially the anticancer actions of zoledronic acid and doxorubicin on PC-3 prostate cancer cells

The Prostate ◽  
2004 ◽  
Vol 59 (2) ◽  
pp. 120-131 ◽  
Author(s):  
Roxane Tenta ◽  
Despina Tiblalexi ◽  
Evangelia Sotiriou ◽  
Peter Lembessis ◽  
Menelaos Manoussakis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Growth Factors ◽  
Zoledronic Acid ◽  
Cancer Cells ◽  
Bone Microenvironment ◽  
Prostate Cancer Cells

Mineralized human primary osteoblast matrices as a model system to analyse interactions of prostate cancer cells with the bone microenvironment

Biomaterials ◽  
2010 ◽  
Vol 31 (31) ◽  
pp. 7928-7936 ◽  
Author(s):  
Johannes C. Reichert ◽  
Verena M.C. Quent ◽  
Leslie J. Burke ◽  
Scott H. Stansfield ◽  
Judith A. Clements ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Model System ◽  
Bone Microenvironment ◽  
Prostate Cancer Cells ◽  
Primary Osteoblast ◽  
Human Primary Osteoblast

scholarly journals N-Myc promotes angiogenesis and therapeutic resistance of prostate cancer by TEM8

2021 ◽  
Vol 38 (10) ◽  
Author(s):  
Mingfeng Li ◽  
Linna Fang ◽  
Louis Boafo Kwantwi ◽  
Guifang He ◽  
Wenwu Luo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Umbilical Vein ◽  
Underlying Mechanism ◽  
Vital Role ◽  
Therapeutic Resistance ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Tubule Formation

AbstractAlthough patients with early localized prostate cancer can survive longer, castration-resistant prostate cancer (CRPC) has gradually emerged with the use of androgen deprivation therapy (ADT). N-Myc and TEM8 play a vital role in the progression of several cancer types. However, the underlying mechanism of how N-Myc and TEM8 promote the progression of prostate cancer remains unclear. In this study, the expression of N-Myc and TEM8 was detected in benign prostatic hyperplasia (BPH) and prostate cancer (PCa) tissues by immunohistochemistry (IHC). LNCaP cell lines were maintained in RPMI 1640 medium supplemented with 10% charcoal-stripped fetal bovine serum. Subsequently, R language software was used to verify our results. Tubule formation assay of human umbilical vein endothelial cell (HUVEC) was conducted to examine the effect of N-Myc and TEM8 overexpression on angiogenesis in prostate cancer cells. IHC results showed a positive correlation between the expression of N-Myc and TEM8 in prostate cancer tissues. Further analysis showed that N-Myc and TEM8 were associated with clinicopathological features and poor prognosis in prostate cancer patients. Moreover, the overexpression of N-Myc and TEM8 promoted proliferation of prostate cancer cells and angiogenesis. Additionally, N-Myc and TEM8 overexpression was associated with therapeutic resistance. We further found that N-Myc promoted angiogenesis and therapeutic resistance in prostate cancer via TEM8. Hence, targeting N-Myc/TEM8 pathway in prostate cancer would be a novel therapeutic strategy to enhance the treatment of prostate cancer patients.

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