scholarly journals The Osteoblastic and Osteoclastic Interactions in Spinal Metastases Secondary to Prostate Cancer

2013 ◽  
Vol 6 ◽  
pp. CGM.S12769 ◽  
Author(s):  
Sathana Dushyanthen ◽  
Davina A.F. Cossigny ◽  
Gerald M.Y. Quan
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Molecular Mechanisms ◽  
Spinal Metastases ◽  
Bone Destruction ◽  
Cord Compression ◽  
Intractable Pain ◽  
Critical Pathway ◽  
Functional Roles ◽  
High Propensity

Prostate cancer (PC) is one of the most common cancers arising in men and has a high propensity for bone metastasis, particularly to the spine. At this stage, it often causes severe morbidity due to pathological fracture and/or metastatic epidural spinal cord compression which, if untreated, inevitably leads to intractable pain, neurological deficit, and paralysis. Unfortunately, the underlying molecular mechanisms driving growth of secondary PC in the bony vertebral column remain largely unknown. Further investigation is warranted in order to identify therapeutic targets in the future. This review summarizes the current understanding of PC bone metastasis in the spine, highlighting interactions between key tumor and bone-derived factors which influence tumor progression, especially the functional roles of osteoblasts and osteoclasts in the bone microenvironment through their interactions with metastatic PC cells and the critical pathway RANK/RANKL/OPG in bone destruction.

scholarly journals The Role of Vascular Endothelial Growth Factor in Metastatic Prostate Cancer to the Skeleton

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Emma Roberts ◽  
Davina A. F. Cossigny ◽  
Gerald M. Y. Quan
Keyword(s):  
Prostate Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Tumour Cell ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Spinal Metastases ◽  
Bone Destruction ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Despite the clinical implication and high incidence of bone and spinal metastases, the molecular mechanisms behind prostate cancer metastasis to bone and spine are not well understood. In this review the molecular mechanisms that may contribute to the highly metastatic phenotype of prostate cancer are discussed. Proangiogenic factors such as vascular endothelial growth factor (VEGF) have been shown to not only aid in the metastatic capabilities of prostate cancer but also encourage the colonization and growth of prostate tumour cells in the skeleton. The importance of VEGF in the complex process of prostate cancer dissemination to the skeleton is discussed, including its role in the development of the bone premetastatic niche, metastatic tumour cell recognition of bone, and bone remodeling. The expression of VEGF has also been shown to be upregulated in prostate cancer and is associated with clinical stage, Gleason score, tumour stage, progression, metastasis, and survival. Due to the multifaceted effect VEGF has on tumour angiogenesis, tumour cell proliferation, and bone destruction, therapies targeting the VEGF pathways have shown promising clinical application and are being investigated in clinical trials.

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 Skeletal-Related Events (SRE) in Prostate Cancer: A Report of Two Cases

2021 ◽  
Vol 57 (3) ◽  
pp. 250
Author(s):  
Anak Agung Ngurah Oka Diatmika ◽  
Sunaryo Hardjowijoto
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Ct Scan ◽  
Specific Antigen ◽  
Compression Fracture ◽  
Serum Testosterone ◽  
Cord Compression ◽  
Thoracic Vertebrae ◽  
Left Femur ◽  
Spinal Mri

A skeletal-related event (SRE) is an event occurring due to bone metastasis in prostate cancer. SREs are usually marked by pain, pathological fractures, spinal cord compression, hypercalcemia, or bone metastasis requiring radiotherapy or operation. Case I: A 64-year-old male was diagnosed with a pathological fracture of the left femur. Thoracal CT scan showed osteoblastic lesions in the thoracal vertebrae, sternum, clavicle, and humeral head. Spinal MRI showed destruction of the cervical to sacral vertebral bodies. The histopathological result with Adenocarcinoma Gleason scores 8 (4+4) and an initial prostate-specific antigen (PSA) level of 689,7 ng/dL. Afterward, subcapsular orchiectomy was performed. However, his PSA level was still high (>100 ng/dL) even after serum testosterone had reached a castration level. The patient died during the first chemotherapy using docetaxel. Case II: A 61-year-old male was diagnosed with inferior paraplegia and neurogenic bladder, paraparesis, urinary retention, and pain in the flank area. Spinal MRI showed a pathological compression fracture of the 8th thoracic vertebrae. Thoracal CT scan showed costal and 8th thoracal vertebrae destruction as well as multiple nodules in the lungs. Histological results with Adenocarcinoma Gleason score 9 (4+5) and an initial PSA level of 750 ng/dL. Afterward, subcapsular orchiectomy was performed. Serum testosterone reached castration level with the lowest PSA concentration of 21.6 g/dL. The patient declined chemotherapy and agreed to palliative treatment. He died one year after diagnosis. A high PSA level (>500 ng/dL) could potentially be used as a predictor for severe SRE.

scholarly journals Regulation of cell–cell adhesion in prostate cancer cells by microRNA-96 through upregulation of E-Cadherin and EpCAM

2019 ◽  
Vol 41 (7) ◽  
pp. 865-874
Author(s):  
Gjendine Voss ◽  
Benedikta S Haflidadóttir ◽  
Helena Järemo ◽  
Margareta Persson ◽  
Tina Catela Ivkovic ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Adhesion ◽  
Bone Metastasis ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Cell Interaction ◽  
Metastatic Progression ◽  
Prostate Cancer Cells ◽  
E Cadherin ◽  
Cell Cell

Abstract Prostate cancer is one of the most common cancers in men, yet the biology behind lethal disease progression and bone metastasis is poorly understood. In this study, we found elevated levels of microRNA-96 (miR-96) in prostate cancer bone metastasis samples. To determine the molecular mechanisms by which miR-96 deregulation contributes to metastatic progression, we performed an Argonaute2-immunoprecipitation assay, in which mRNAs associated with cell–cell interaction were enriched. The expression of two cell adhesion molecules, E-Cadherin and EpCAM, was upregulated by miR-96, and potential targets sites were identified in the coding sequences of their mRNAs. We further showed that miR-96 enhanced cell–cell adhesion between prostate cancer cells as well as their ability to bind to osteoblasts. Our findings suggest that increased levels of miR-96 give prostate cancer cells an advantage at forming metastases in the bone microenvironment due to increased cell–cell interaction. We propose that miR-96 promotes bone metastasis in prostate cancer patients by facilitating the outgrowth of macroscopic tumours in the bone.

scholarly journals Management of Myeloma Bone Lesions

2021 ◽  
Vol 22 (7) ◽  
pp. 3389
Author(s):  
Jeng-Shiun Du ◽  
Chia-Hung Yen ◽  
Chin-Mu Hsu ◽  
Hui-Hua Hsiao
Keyword(s):  
Bone Disease ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Bone Destruction ◽  
Cord Compression ◽  
Bone Diseases ◽  
Novel Agents ◽  
Bone Lesions ◽  
Skeletal Involvement ◽  
Skeletal Related Events

Multiple myeloma (MM) is a B-cell neoplasm characterized by clonal plasma–cell proliferation. The survival and prognosis of this condition have been significantly improved by treatment with active anti-MM drugs such as bortezomib or lenalidomide. Further, the discovery of novel agents has recently paved the way for new areas of investigation. However, MM, including myeloma-related bone diseases, remains fatal. Bone disease or bone destruction in MM is a consequence of skeletal involvement with bone pain, spinal cord compression, and bone fracture resulting from osteolytic lesions. These consequences affect disease outcomes, including patients’ quality of life and survival. Several studies have sought to better understand MM bone disease (MBD) through the classification of its molecular mechanisms, including osteoclast activation and osteoblast inhibition. Bisphosphonates and the receptor activator of the nuclear factor-kappa B (NF-κB) ligand (RANKL) inhibitor, denosumab, prevent skeletal-related events in MM. In addition, several other bone-targeting agents, including bone-anabolic drugs, are currently used in preclinical and early clinical evaluations. This review summarizes the current knowledge of the pathogenesis of MBD and discusses novel agents that appear very promising and will soon enter clinical development.

Characterization of metastatic spinal cord compression from prostate cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 248-248
Author(s):  
Jianbo Wang
Keyword(s):  
Prostate Cancer ◽  
Spinal Cord ◽  
Bone Metastasis ◽  
Clinical Outcome ◽  
Gleason Score ◽  
Spinal Cord Compression ◽  
Thoracic Spine ◽  
Radiation Treatment ◽  
Cord Compression ◽  
Anatomical Site

248 Background: Spinal cord compression (SCC) is one of the most debilitating conditions in metastatic prostate cancer patients (pts). A comprehensive analysis of pts could shed lights on predisposing factors and help with devising new ways for early detection and prompt treatment. Methods: 52 pts with magnetic resonance imaging-confirmed metastatic SCC from prostate cancer were identified at MD Anderson Cancer Center. Characteristics including age, anatomical site, Gleason score, overall survival(OS), time to diagnosis of SCC, underlying gene mutations, numbers of bone metastasis, number of lines of treatment and clinical outcome were analyzed. Results: 96.15% of SCC occurred in thoracic spine in comparison to 74% as reported previously. At the time of diagnosis of SCC, median age is 70 years, median OS is 1537 days, median time to development of SCC is 1222.5 days, median lines of systemic treatment is 4, median PSA value is 66.4, 100% of pts have a Gleason score above 7, 94% of pts have >4 bone metastasis, roughly 20% of pts had visceral metastases. 55% of 9 evaluable pts harbored P53 gene mutation. About 80% of pts received radiation treatment; 17% of pts received surgery; 49% of pts had fair clinical outcome after treatment (Table). Conclusions: The observed predominance of SCC in thoracic spine (96.15%) suggests an underlying mechanism governing development of SCC in preferential sites. Further research to define this mechanism will help with prevention, detection and treatment of SCC. Additionally, characterized potential predictive factors (Gleason score≥7, >4 bone mets, presence of P53 mutation) could be used to develop an algorithm to improve the management of SCC.[Table: see text]

scholarly journals Identification of Key Gene Signatures Associated With Bone Metastasis in Castration-Resistant Prostate Cancer Using Co-Expression Analysis

2021 ◽  
Vol 10 ◽  
Author(s):  
Zhongxiang Yu ◽  
Hanlin Zou ◽  
Huihao Wang ◽  
Qi Li ◽  
Dong Yu
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Bone Metastasis ◽  
Molecular Mechanisms ◽  
Bone Development ◽  
Tumor Development ◽  
Enrichment Analysis ◽  
Castration Resistant Prostate Cancer ◽  
Metastatic Colonization ◽  
Castration Resistant

About 80–90% of castration-resistant prostate cancer (CRPC) patients would develop bone metastasis. However, the molecular mechanisms of bone metastasis are still not clear. This study aimed to detect the differences between the tumor and normal samples in bone after metastatic colonization. Four transcriptional datasets (GSE32269, GSE101607, GSE29650, and GSE74685) were obtained from the GEO database. 1983 differentially expressed genes (DEGs) were first identified between tumor and normal marrow samples in GSE32269. Most of the top 10 up-regulated DEGs are related with prostate cancer, and the top 10 down-regulated DEGs are mainly related with bone development. Seven co-expression modules were then detected based on the 1469 DEGs shared by the four datasets. Three of them were found highly preserved among the four datasets. Enrichment analysis showed that the three modules were respectively enriched in Cell adhesion molecules (CAMs), Leukocyte transendothelial migration and cell cycle, which might play significantly important roles in the tumor development in bone marrow. Ten, 17, and 99 hub genes for each module were then identified. And four genes (C3AR1, IL10RA, LY86, and MS4A6A) were detect to be tightly related to progression of bone metastatic CRPC. ROC curve was plotted and AUC was calculated to distinguish tumor and normal bone marrow samples as well as bone and non-bone metastatic CRPCs. The present study identified key genes and modules involved in bone metastatic CRPCs, which may provide new insights and biomarkers for understanding of the molecular mechanisms of bone metastatic CRPC.

scholarly journals Androgen Receptor-Related Non-coding RNAs in Prostate Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Yongyong Yang ◽  
Kilia Y. Liu ◽  
Qi Liu ◽  
Qi Cao
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
The United States ◽  
Castration Resistant Prostate Cancer ◽  
Functional Roles ◽  
Castration Resistant ◽  
Number Of Patients ◽  
Non Coding Rnas

Prostate cancer (PCa) is the second leading cause of cancer-related death among men in the United States. Androgen receptor (AR) signaling is the dominant oncogenic pathway in PCa and the main strategy of PCa treatment is to control the AR activity. A large number of patients acquire resistance to Androgen deprivation therapy (ADT) due to AR aberrant activation, resulting in castration-resistant prostate cancer (CRPC). Understanding the molecular mechanisms underlying AR signaling in the PCa is critical to identify new therapeutic targets for PCa patients. The recent advances in high-throughput RNA sequencing (RNA-seq) techniques identified an increasing number of non-coding RNAs (ncRNAs) that play critical roles through various mechanisms in different diseases. Some ncRNAs have shown great potentials as biomarkers and therapeutic targets. Many ncRNAs have been investigated to regulate PCa through direct association with AR. In this review, we aim to comprehensively summarize recent findings of the functional roles and molecular mechanisms of AR-related ncRNAs as AR regulators or targets in the progression of PCa.

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