Bone Metastasis: Molecular Mechanisms Implicated in Tumour Cell Dormancy in Breast and Prostate Cancer

2015 ◽  
Vol 15 (6) ◽  
pp. 469-480 ◽  
Author(s):  
Lewis Quayle ◽  
Penelope Ottewell ◽  
Ingunn Holen
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Tumour Cell ◽  
Molecular Mechanisms ◽  
Breast And Prostate Cancer ◽  
Cell Dormancy

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 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 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 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 The Trend of Dental Check-Up And Incidence of Dental Complications Following The Use of Bone Modifying Agents In Patients With Metastatic Breast And Prostate Cancer: Analysis of Data From The Korean National Health Insurance Service

2022 ◽  
Author(s):  
Ah Reum Lim ◽  
Wonse Park ◽  
Seok Joo Moon ◽  
Min Sun Kim ◽  
Soohyeon Lee
Keyword(s):  
Prostate Cancer ◽  
Health Insurance ◽  
Bone Metastasis ◽  
National Health Insurance ◽  
National Health ◽  
Dental Treatment ◽  
Metastatic Cancer ◽  
Metastatic Breast ◽  
Korean National Health Insurance ◽  
Breast And Prostate Cancer

Abstract Purpose: Bone-modifying agents (BMAs) are key components in the management of cancer patients with bone metastasis. Despite their clinical benefits, the use of BMAs is associated with adverse dental events including medication-related osteonecrosis of the jaw (MRONJ). This study investigated the rate of preoperative dental surveillance to reduce the incidence of adverse dental events including MRONJ after BMA treatment in patients with bone metastasis from breast and prostate cancer. Methods: Data, including age, cancer diagnosis, administered BMAs, and adverse dental events during cancer treatment, of patients with bone metastasis from breast and prostate cancer who received at least one infusion of BMA between 2007 and 2019 were extracted from the Korean National Health Insurance Service (KNHIS) dataset. Results: Of the 15357 patients who received BMAs, 1706 patients (11.1%) underwent dental check-ups before BMA treatment. The proportion of patients receiving dental check-ups increased from 4.4% in 2007 to 16.7% in 2019. Referral for dental check-up was more frequent in clinics and primary hospitals than in tertiary hospitals, and from the departments of internal medicine and urology than from the department of general surgery, regardless of the patient's health insurance status. After BMA treatment, 3328 patients (21.6%) developed adverse dental events, including tooth extraction (73.0%), abscess (16.9%), acute periodontitis (5.3%), acute pericoronitis (2.6%), and MRONJ (2.2% of 3328, 0.5% of 15357). Conclusions: Considering the long treatment period in patients with metastatic cancer, coordination between dentists and oncologists is necessary to ensure appropriate dental treatment before the initiation of BMAs.

scholarly journals Incidence and Prognosis of Bone Metastases in Common Solid Cancers at Initial Diagnosis: A Population-Based Study

2020 ◽  
Author(s):  
Jing Zhang ◽  
Qingde Wa ◽  
Song Hong ◽  
Dongfeng Cai ◽  
Jiachen Peng
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Nasopharyngeal Carcinoma ◽  
Bone Metastases ◽  
Patient Survival ◽  
Treatment Options ◽  
Population Based ◽  
Initial Diagnosis ◽  
Breast And Prostate Cancer ◽  
Primary Type

Abstract Background Bone is one of the most common sites of advanced tumors. However, there is currently a lack of population-based surveys for the incidence and prognosis of bone metastases in common solid cancers.Methods Patients with 12 types of primary cancer and bone metastases at initial diagnosis between 2010 and 2015 were identified using the Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan-Meier method and Cox logistic regression were conducted to analyze survival and the effect of bone metastases on different cancers.Results We included 89,782 patients with bone metastases at cancer diagnosis. Lung cancer had the highest incidence (17.61%) of bone metastases at diagnosis in any stage, followed by liver cancer (6.29%), nasopharyngeal carcinoma (6.22%) and renal cancer (5.19%). Among patients with breast and prostate cancer, only 3.4% and 4.39%, respectively, were identified as having bone metastases at diagnosis. Breast cancer (32.1%), prostate cancer (25.2%), thyroid cancer (46.8%) and nasopharyngeal carcinoma (24.8%) patients with only bone metastasis have an over 20% five-year survival rate. Compared with patients at a stage previous to metastasis, bone metastasis significantly increased the risk of mortality and reduced survival time, especially for patients with prostate cancer (HR: 19.64, 95% CI 18.36 to 21.02). Concomitant other organ metastases make patient survival worse. Regarding the metastases of prostate cancer, bone metastases are the main type, while for colorectal cancer, bone metastases and concomitant visceral metastases mainly occur.Conclusions The findings of this study provide estimates of the incidence and prognosis of patients with bone metastases during the initial diagnosis of common solid cancers. In addition, we also clarified the degree to which bone metastasis affects patient survival. Patient prognosis depends on the primary type of cancer. These results can be used as a reference for the screening of metastases, and the optimization of personalized treatment options to improve the quality of life and survival of patients.

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