The Roles of Bone Marrow-Resident Cells as a Microenvironment for Bone Metastasis

2020 ◽  
pp. 57-72 ◽  
Author(s):  
Yusuke Shiozawa
Keyword(s):  
Bone Marrow ◽  
Bone Metastasis

scholarly journals Long non‐coding RNA NORAD promotes the prostate cancer cell extracellular vesicle release via microRNA-541-3p-regulated PKM2 to induce bone metastasis of prostate cancer

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Chuan-yi Hu ◽  
Juan Chen ◽  
Xin-hua Qin ◽  
Pan You ◽  
Jie Ma ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Bone Metastasis ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Marrow Stromal Cells ◽  
Downstream Target ◽  
Non Coding Rna ◽  
Target Molecules ◽  
Long Non Coding Rna

Abstract Background Bone metastasis is the leading cause of mortality and reduced quality of life in patients with metastatic prostate cancer (PCa). Long non-coding RNA activated by DNA damage (NORAD) has been observed to have an abnormal expression in various cancers. This article aimed to explore the molecular mechanism underlying the regulatory role of NORAD in bone metastasis of PCa. Methods NORAD expression in clinical PCa tissues and cell lines was detected with the application of qRT-PCR. Cancer cells were then transfected with plasmids expressing NORAD, after which Transwell assay and CCK-8 assay were carried out to detect proliferation, migration, and bone metastasis of PCa. NORAD downstream target molecules were screened through bioinformatics analysis, followed by further verification using dual luciferase assay. Extracellular vesicles (EVs) were labeled with PKH67 and interacted with bone marrow stromal cells. The gain- and loss-function method was applied to determine the internalization and secretion of PCa cells-derived EVs under the intervention of downstream target molecules or NORAD. Results PCa tissues and cell lines were observed to have a high expression of NORAD, particularly in tissues with bone metastasis. NORAD knockdown resulted in reduced secretion and internalization of EVs, and suppressed proliferation, migration, and bone metastasis of PCa cells. It was indicated that NORAD interacted with miR-541-3p, leading to the upregulation of PKM2. Forced expression of PKM2 promoted the transfer of PKH67-labeled EVs to bone marrow stromal cells. Conclusions NORAD might serve as a ceRNA of miR-541-3p to promote PKM2 expression, thereby enhancing the development of bone metastasis in PCa by promoting internalization and transfer of EVs of cancer cells, providing an insight into a novel treatment for the disorder.

scholarly journals Integrin alpha5 in human breast cancer is a mediator of bone metastasis and a therapeutic target for the treatment of osteolytic lesions

Oncogene ◽  
2021 ◽  
Author(s):  
Francesco Pantano ◽  
Martine Croset ◽  
Keltouma Driouch ◽  
Natalia Bednarz-Knoll ◽  
Michele Iuliani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Bone Metastasis ◽  
Tumor Cell ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Osteolytic Lesions ◽  
Cell Colonization

AbstractBone metastasis remains a major cause of mortality and morbidity in breast cancer. Therefore, there is an urgent need to better select high-risk patients in order to adapt patient’s treatment and prevent bone recurrence. Here, we found that integrin alpha5 (ITGA5) was highly expressed in bone metastases, compared to lung, liver, or brain metastases. High ITGA5 expression in primary tumors correlated with the presence of disseminated tumor cells in bone marrow aspirates from early stage breast cancer patients (n = 268; p = 0.039). ITGA5 was also predictive of poor bone metastasis-free survival in two separate clinical data sets (n = 855, HR = 1.36, p = 0.018 and n = 427, HR = 1.62, p = 0.024). This prognostic value remained significant in multivariate analysis (p = 0.028). Experimentally, ITGA5 silencing impaired tumor cell adhesion to fibronectin, migration, and survival. ITGA5 silencing also reduced tumor cell colonization of the bone marrow and formation of osteolytic lesions in vivo. Conversely, ITGA5 overexpression promoted bone metastasis. Pharmacological inhibition of ITGA5 with humanized monoclonal antibody M200 (volociximab) recapitulated inhibitory effects of ITGA5 silencing on tumor cell functions in vitro and tumor cell colonization of the bone marrow in vivo. M200 also markedly reduced tumor outgrowth in experimental models of bone metastasis or tumorigenesis, and blunted cancer-associated bone destruction. ITGA5 was not only expressed by tumor cells but also osteoclasts. In this respect, M200 decreased human osteoclast-mediated bone resorption in vitro. Overall, this study identifies ITGA5 as a mediator of breast-to-bone metastasis and raises the possibility that volociximab/M200 could be repurposed for the treatment of ITGA5-positive breast cancer patients with bone metastases.

scholarly journals Ras and Wnt Interaction Contribute in Prostate Cancer Bone Metastasis

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2380 ◽  
Author(s):  
Shian-Ren Lin ◽  
Ntlotlang Mokgautsi ◽  
Yen-Nien Liu
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Bone Metastasis ◽  
Signaling Pathways ◽  
Late Stage ◽  
Ras Signaling ◽  
Cancer Death ◽  
Metastatic Site ◽  
Cancer Types ◽  
Cytological Changes

Prostate cancer (PCa) is one of the most prevalent and malignant cancer types in men, which causes more than three-hundred thousand cancer death each year. At late stage of PCa progression, bone marrow is the most often metastatic site that constitutes almost 70% of metastatic cases of the PCa population. However, the characteristic for the osteo-philic property of PCa is still puzzling. Recent studies reported that the Wnt and Ras signaling pathways are pivotal in bone metastasis and that take parts in different cytological changes, but their crosstalk is not well studied. In this review, we focused on interactions between the Wnt and Ras signaling pathways during each stage of bone metastasis and present the fate of those interactions. This review contributes insights that can guide other researchers by unveiling more details with regard to bone metastasis and might also help in finding potential therapeutic regimens for preventing PCa bone metastasis.

scholarly journals Radiation-induced occult insufficiency fracture or bone metastasis after radiotherapy for cervical cancer? The nomogram based on quantitative apparent diffusion coefficients for discrimination

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Xi Zhong ◽  
Huali Jiang ◽  
Hui Mai ◽  
Jialin Xiang ◽  
Jiansheng Li ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Bone Marrow ◽  
Bone Metastasis ◽  
Bone Metastases ◽  
Predictive Value ◽  
Bone Lesions ◽  
Potential Value ◽  
Apparent Diffusion ◽  
Adc Values ◽  
Radiation Induced

Abstract Background Radiation-induced insufficiency fractures (IF) is frequently occult without fracture line, which may be mistaken as metastasis. Quantitative apparent diffusion coefficient (ADC) shows potential value for characterization of benign and malignant bone marrow diseases. The purpose of this study was to develop a nomogram based on multi-parametric ADCs in the differntiation of occult IF from bone metastasis after radiotherapy (RT) for cervical cancer. Methods This study included forty-seven patients with cervical cancer that showed emerging new bone lesions in RT field during the follow-up. Multi-parametric quantitative ADC values were measured for each lesion by manually setting region of interests (ROIs) on ADC maps, and the ROIs were copied to adjacent normal muscle and bone marrow. Six parameters were calculated, including ADCmean, ADCmin, ADCmax, ADCstd, ADCmean ratio (lesion/normal bone) and ADCmean ratio (lesion/muscle). For univariate analysis, receiver operating characteristic curve (ROC) analysis was performed to assess the performance. For combined diagnosis, a nomogram model was developed by using a multivariate logistic regression analysis. Results A total of 75 bone lesions were identified, including 48 occult IFs and 27 bone metastases. There were significant differences in the six ADC parameters between occult IFs and bone metastases (p < 0.05), the ADC ratio (lesion/ muscle) showed an optimal diagnostic efficacy, with an area under ROC (AUC) of 0.887, the sensitivity of 95.8%, the specificity of 81.5%, respectively. Regarding combined diagnosis, ADCstd and ADCmean ratio (lesion/muscle) were identified as independent factors and were selected to generate a nomogram model. The nomogram model showed a better performance, yielded an AUC of 0.92, the sensitivity of 91.7%, the specificity of 96.3%, positive predictive value (PPV) of 97.8% and negative predictive value (NPV) of 86.7%, respectively. Conclusions Multi-parametric ADC values demonstrate potential value for differentiating occult IFs from bone metastasis, a nomogram based on the combination of ADCstd and ADCmean ratio (lesion/muscle) may provide an improved classification performance.

Bone Marrow Niche: Role of Different Cells in Bone Metastasis

2018 ◽  
Vol 4 (2) ◽  
pp. 80-87
Author(s):  
Terhi J. Heino ◽  
Jorma A. Määttä
Keyword(s):  
Bone Marrow ◽  
Bone Metastasis ◽  
Bone Marrow Niche

scholarly journals Microenvironmental IL1β promotes breast cancer metastatic colonisation in the bone via activation of Wnt signalling

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Rachel Eyre ◽  
Denis G. Alférez ◽  
Angélica Santiago-Gómez ◽  
Kath Spence ◽  
James C. McConnell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Bone Metastasis ◽  
Bone Metastases ◽  
Colony Formation ◽  
Breast Cancer Cells ◽  
Wnt Signalling ◽  
Early Event ◽  
Metastatic Lesions ◽  
Breast Cancer Bone Metastasis

Abstract Dissemination of tumour cells to the bone marrow is an early event in breast cancer, however cells may lie dormant for many years before bone metastases develop. Treatment for bone metastases is not curative, therefore new adjuvant therapies which prevent the colonisation of disseminated cells into metastatic lesions are required. There is evidence that cancer stem cells (CSCs) within breast tumours are capable of metastasis, but the mechanism by which these colonise bone is unknown. Here, we establish that bone marrow-derived IL1β stimulates breast cancer cell colonisation in the bone by inducing intracellular NFkB and CREB signalling in breast cancer cells, leading to autocrine Wnt signalling and CSC colony formation. Importantly, we show that inhibition of this pathway prevents both CSC colony formation in the bone environment, and bone metastasis. These findings establish that targeting IL1β-NFKB/CREB-Wnt signalling should be considered for adjuvant therapy to prevent breast cancer bone metastasis.

scholarly journals Human Bone Marrow–Derived MSCs Can Home to Orthotopic Breast Cancer Tumors and Promote Bone Metastasis

2010 ◽  
Vol 70 (24) ◽  
pp. 10044-10050 ◽  
Author(s):  
Robert H. Goldstein ◽  
Michaela R. Reagan ◽  
Kristen Anderson ◽  
David L. Kaplan ◽  
Michael Rosenblatt
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Bone Metastasis ◽  
Human Bone ◽  
Human Bone Marrow

Radium 223 treatment in metastatic castrate-resistant prostate cancer: Impact of sequencing on survival—Real-world outcomes from a single United Kingdom center.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 223-223 ◽  
Author(s):  
Xue Yan Jiang ◽  
Sarah Atkinson ◽  
Sam Cuming ◽  
Alexander Burns ◽  
Rachel Anne Pearson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Bone Metastasis ◽  
Systemic Treatment ◽  
Survival Outcomes ◽  
Prior Chemotherapy ◽  
Radium 223 ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
The Impact

223 Background: Radium 223 (Ra-223) is a FDA and EMA approved alpha particle radiopharmaceutical used to treat men with metastatic castrate resistant prostate cancer (mCRPC) with symptomatic bone metastasis. In view of emerging systemic options, new EMA 2018 licence indication is for 3rd line onwards. We aim to evaluate the impact of systemic therapy sequencing on survival outcomes from a heterogeneous cohort of 228 patients treated with Ra-223 in a single UK centre. Methods: We prospectively collected data from 228 men underwent Ra-223 therapy for mCRPC between April 2014 and August 2018. Survival outcomes in relation to sequence of systemic treatment used prior to Ra-223 were analysed. Results: Medium age = 72 (51-87) years. Most patients (n = 142, 69%) received at least one systemic agent prior to Ra-223: docetaxel and/or cabaxitaxel chemotherapy (n = 60, 29%), abiraterone (n = 62, 30.1%) and enzalutamide (n = 67, 32.5%) in various sequences. No patients received concurrent Ra-223 /systemic treatment other than LHRH analogue. Key findings are summarized in table below. Conclusions: Our data demonstrated better survival trend in patients who received Ra-223 early. Patients who received prior chemotherapy have worse survival compared with those who were chemo-naïve likely due to bone marrow depletion. Ra-223 should not be offered to patients who have already had both cabaxitaxel and docetaxel as their medium survival is too poor to justify a treatment which takes 6 months to complete.[Table: see text]

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