The active role of osteoporosis in the interaction between osteoblasts and bone metastases

Pagani, Stefania; Fini, Milena; Giavaresi, Gianluca; Salamanna, Francesca; Borsari, Veronica

doi:10.1016/j.bone.2015.06.002

Cited by 18 publications

(11 citation statements)

References 30 publications

(5 reference statements)

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“…The ultimate results are bone volume loss, bone strength decrease and a high risk of bone fracture 30, 31 . Hif - 1α is the most important regulator of oxygen homeostasis in mammals and controls physiological and pathological neo-angiogenesis 32 .…”

Section: Discussionmentioning

confidence: 99%

CD31hiEmcnhi Vessels Support New Trabecular Bone Formation at the Frontier Growth Area in the Bone Defect Repair Process

Wang

Gao

Cheng

et al. 2017

Sci Rep

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CD31hiEmcnhi vessels were a subtype of vessels in the murine skeletal system, with high levels of platelet and endothelial cell adhesion molecule-1 (PECAM-1/CD31) and endomucin (Emcn). They were reported coupling angiogenesis and osteogenesis during bone development. We investigated the distribution of these vessels in rat tibiae and their temporal and spatial distribution during the bone defect repair process to improve our understanding of the importance of these vessels. We confirmed that CD31hiEmcnhi vessels were specially distributed around the trabecular bones near metaphysis and endosteum in rat tibiae. At 3 days post bone injury, CD31hiEmcnhi vessels proliferated and were extensively distributed across the entire repair area. At 7 and 14 days post-injury, these vessels decreased but were specially distributed around the growing trabecular bones near the frontier growth area, suggesting that these vessels support new bone formation. The distribution of CD31hiEmcnhi vessels and the transcriptions of Hif-1α and VEGFA, as well as BMP2 and Osterix decreased at 7 and 14 days post-injury under osteoporotic conditions, in combination with insufficient osteogenesis. Our research is of great significance to help understand the important role of CD31hiEmcnhi vessels in supporting new trabecular bones formation during bone defect repair process.

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Section: Discussionmentioning

confidence: 99%

CD31hiEmcnhi Vessels Support New Trabecular Bone Formation at the Frontier Growth Area in the Bone Defect Repair Process

Wang

Gao

Cheng

et al. 2017

Sci Rep

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“…Also, by using a humanized breast cancer bone metastasis model, increased levels of IL-8 were seen, in particular under osteoporotic conditions [43]. Metastatic breast cancer cells directly induce osteoblasts to express increased levels of IL-8 [54,56,68,[71][72][73], especially under osteoporotic conditions [71], in the presence or in absence of the RANK/RANKL pathway [56]. Osteoblasts release several growth factors and, among them, TGF-β1 (Transforming Growth Factor -β1) is an important contributor to extracellular signal-related kinase (ERK), p38, and c-Jun N-terminal kinase (JNK) activation [72], which lead to the activation of activator protein 1(AP-1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) on the IL-8 promoter, and which initiate IL-8 release, thus promoting breast cancer cell migration and osteoclastogenesis [21,54,69,72].…”

Section: Il-8mentioning

confidence: 99%

What Is the Role of Interleukins in Breast Cancer Bone Metastases? A Systematic Review of Preclinical and Clinical Evidence

Salamanna

Borsari

Contartese

et al. 2019

Cancers

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Breast cancer cells produce stimulators of bone resorption known as interleukins (ILs). However, data on the functional roles of ILs in the homing of metastatic breast cancer to bone are still fragmented. A systematic search was carried out in three databases (PubMed, Scopus, Web of Science Core Collection) to identify preclinical reports, and in three clinical registers (ClinicalTrials.gov, World Health Organization (WHO) International Clinical Trials Registry Platform, European Union (EU) Clinical Trials Register) to identify clinical trials, from 2008 to 2019. Sixty-seven preclinical studies and 11 clinical trials were recognized as eligible. Although preclinical studies identified specific key ILs which promote breast cancer bone metastases, which have pro-metastatic effects (e.g., IL-6, IL-8, IL-1β, IL-11), and whose inhibition also shows potential preclinical therapeutic effects, the clinical trials focused principally on ILs (IL-2 and IL-12), which have an anti-metastatic effect and a potential to generate a localized and systemic antitumor response. However, these clinical trials are yet to post any results or conclusions. This inconsistency indicates that further studies are necessary to further develop the understanding of cellular and molecular relations, as well as signaling pathways, both up-and downstream of ILs, which could represent a novel strategy to treat tumors that are resistant to standard care therapies for patients affected by breast cancer bone disease.An initial literature search found 905 references, of which 151 articles were recognized using the PubMed database, 481 articles were recognized using Scopus, and 273 articles were found in the Web of Science Core Collection. Subsequently, the resulting references were submitted to a public reference manager (Mendeley 1.17.11) to eliminate duplicate articles, obtaining 666 articles. From the 666 articles obtained, after exclusion, 116 full-text articles were evaluated, of which 67 met the inclusion criteria. The 560 studies excluded from this review were excluded because they were meeting reports, reviews, book chapters, and case reports, and/or because they reported IL roles in primary breast tumor, as well as in lung, liver, and pulmonary metastasis, leukemia, osteosarcoma, ovarian tumor, melanoma, prostate cancer, autoimmune arthritis related to breast cancer, and other pathological conditions; however, they did not reveal the favorable development of bone metastases from breast cancer. In addition, we excluded studies where IL profiling was derived from breast cancer metastatic patients that were not grouped/analyzed based on the site of metastasis, and where breast cancer bone metastases were evaluated, but no IL roles/functions were examined. Finally, we also eliminated studies where responses to specific therapy (not IL-based) for breast cancer bone metastasis were analyzed, studies that evaluated the contributions of the sensory signaling pathways to neuropathic pain induced by breast cancer bone metastases, and studies on chronic s...

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“…The process of cancer metastases, following tumor growth at the primary site of origin, involves intravasation and survival in the bloodstream, arrest, extravasation and finally establishment, by invasion and angiogenesis, at a distant site [17–18]. Tumor cells that metastasize in bone induce destructive osteolytic and/or bone forming osteoblastic lesions [12, 19] and ‘teach’ this affected bone microenvironment to produce factors that stimulate tumor cell growth [20–21]. In general, once bone metastases are present, patient survival is dramatically reduced.…”

Section: Introductionmentioning

confidence: 99%

A systematic review on in vitro 3D bone metastases models: A new horizon to recapitulate the native clinical scenario?

et al. 2016

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While the skeleton is not the only organ where metastasis can occur, it is one of the preferred sites, with a significant impact in patients' quality of life. With the aim of delineating the cellular and molecular mechanisms of bone metastasis, numerous studies have been employed to identify any contributing factors that trigger cancer progression. One of the major limitations of studying cancer-bone metastasis is the multifaceted nature of the native bone environment and the lack of reliable, simple, and not expensive models that strictly mimic the biological processes occurring in vivo allowing a correct translation of results. Currently, with the growing acceptance of in vitro models as effective tools for studying cancer biology, three-dimensional (3D) models have emerged as a compromise between two-dimensional cultures of isolated cancer cells and the complexity of human cancer xenografts in immunocompromised animal hosts. This descriptive systematic literature review summarizes the current status of advanced and alternative 3D in vitro bone metastases models. We have also reviewed the strategies employed by researchers to set-up these models with special reference to recent promising developments trying to better replicate the complexity and heterogeneity of a human metastasis in situ, with an outlook at their use in medicine. All these aspects will greatly contribute to the existing knowledge on bone metastases, providing a specific link to clinical scenarios and thus making 3D in vitro bone metastasis models an attractive tool for multidisciplinary experts.

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The active role of osteoporosis in the interaction between osteoblasts and bone metastases

Cited by 18 publications

References 30 publications

CD31hiEmcnhi Vessels Support New Trabecular Bone Formation at the Frontier Growth Area in the Bone Defect Repair Process

CD31hiEmcnhi Vessels Support New Trabecular Bone Formation at the Frontier Growth Area in the Bone Defect Repair Process

What Is the Role of Interleukins in Breast Cancer Bone Metastases? A Systematic Review of Preclinical and Clinical Evidence

A systematic review on in vitro 3D bone metastases models: A new horizon to recapitulate the native clinical scenario?

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