Lung tumor cells inhibit bone mineralization and osteoblast activity

Berent, Taylor E.; Dorschner, Jessica M.; Craig, Theodore A.; Drake, Matthew T.; Kumar, Rajiv

doi:10.1016/j.bbrc.2019.09.045

Cited by 10 publications

(3 citation statements)

References 40 publications

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“…It has been suggested that poor mineralization can promote the adhesion of cancer cells, resulting in the development of cancer [ 27 ]. Moreover, lung cancer cells also can inhibit bone mineralization, which may be related to the bone metastasis of lung cancer [ 28 ]. It is widely known that nitrogen is essential for the growth of cancer and immune cells [ 29 – 31 ].…”

Section: Discussionmentioning

confidence: 99%

Selection of lncRNAs That Influence the Prognosis of Osteosarcoma Based on Copy Number Variation Data

Zhang

Huang

Zhu

et al. 2022

Journal of Oncology

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Osteosarcoma is the most common primary malignancy in the musculoskeletal system. It is reported that copy number variation- (CNV-) derived lncRNAs contribute to the progression of osteosarcoma. However, whether CNV-derived lncRNAs affect the prognosis of osteosarcoma remains unclear. Here, we obtained osteosarcoma-related CNV data and gene expression profiles from The Cancer Genome Atlas (TCGA) database. CNV landscape analysis indicated that copy number amplification of lncRNAs was more frequent than deletion in osteosarcoma samples. Thirty-four CNV-lncRNAs with DNA-CNV frequencies greater than 30% and their corresponding 294 mRNAs were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analyses revealed that these mRNAs were mainly enriched in olfaction, olfactory receptor activity, and olfactory transduction processes. Furthermore, we predicted that a total of 23 genes were cis-regulated by 16 CNV-lncRNAs, while 30 transcription factors (TFs) were trans-regulated by 5 CNV-lncRNAs. Through t -tests, univariate Cox regression analysis, and the least absolute shrinkage and selection operator (LASSO), we constructed a CNV-related risk model including 3 lncRNAs (AC129492.1, PSMB1, and AC037459.4). The Kaplan-Meier (K-M) curves indicated that patients with high-risk scores showed poor prognoses. The areas under the receiver operating characteristic (ROC) curves (AUC) for predicting 3-, 5-, and 7-year overall survival (OS) were greater than 0.7, showing a satisfactory predictive efficiency. Gene set enrichment analysis (GSEA) revealed that the prognostic signature was intimately linked to skeletal system development, immune regulation, and inflammatory response. Collectively, our study developed a novel 3-CNV-lncRNA prognostic signature that would provide theoretical guidance for the clinical prognostic management of osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

Selection of lncRNAs That Influence the Prognosis of Osteosarcoma Based on Copy Number Variation Data

Zhang

Huang

Zhu

et al. 2022

Journal of Oncology

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“…Cytokines (such as PTHrP, interleukin (IL)-1, IL-6, and IL-8) derived from cancer cells could activate osteoclasts and subsequently activate the RANKL/RANK pathway which had been proven to be correlated with poor prognosis in cancer patients ( 30 , 31 ). Animal experiments have shown that reduced bone mineral density, trabecular thickness, and mineralization can be observed in NSCLC mice in the absence of tumor cell metastasis ( 32 ). From another point of view, BMD not only reflected the general condition and nutritional status of patients but was also associated with tumor progression to a degree.…”

Section: Discussionmentioning

confidence: 99%

Bone mineral density as an individual prognostic biomarker in NSCLC patients treated with immune checkpoint inhibitors

Lou,

Gong,

et al. 2024

Front. Immunol.

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BackgroundImmune checkpoint inhibitors (ICIs) have left a deep impression in the treatment of non-small cell lung cancer (NSCLC), however, not all patients benefit from it. The purpose of this study was to investigate the prognostic value of baseline bone mineral density (BMD) derived from chest computed tomography (CT) scans in NSCLC patients treated with ICIs.MethodsThis study included patients with advanced NSCLC who underwent ICI treatment at the Wuhan Union Hospital from March 2020 to October 2022. Baseline BMD was evaluated at non-contrast chest CT at the level of first lumbar vertebra. Patients were divided into BMD-lower group and BMD-higher group according to the optimal cutoff value calculated by X-tile software. Baseline characteristics of the two groups were compared and variables between the two groups were balanced by propensity score matching (PSM) analysis. We calculated the objective response rate (ORR) and disease control rate (DCR) of the two groups and analyzed overall survival (OS) and progression-free survival (PFS) using BMD and other clinical indexes through Cox regression models and Kaplan-Meier survival curves.ResultsA total of 479 patients were included in this study, and all patients were divided into BMD-lower group (n=270) and BMD-higher group (n=209). After PSM analysis, each group consisted of 150 patients. ORR (43.3% vs. 43.5% before PSM, P = 0.964; 44.7% vs. 44.7% after PSM, P = 1.000) and DCR (91.1% vs. 94.3% before PSM, P = 0.195; 93.3% vs. 96.7% after PSM, P =0.190) were similar in two groups. There was no statistically significant relationship between BMD degree and PFS before (16.0 months vs. 18.0 months, P = 0.067) and after PSM analysis (17.0 months vs. 19.0 months, P = 0.095). However, lower BMD was associated with shorter OS both before (20.5 months vs. 23.0 months, P< 0.001) and after PSM analysis (20.0 months vs. 23.0 months, P = 0.008).ConclusionLower baseline BMD is associated with worse clinical outcomes in NSCLC patients treated with ICIs. As a reliable and easily obtained individual prognostic biomarker, BMD can become a routine detection indicator before immunotherapy.

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“…QRT-PCR and Western blot results showed that the mRNAs and proteins expression of RUNX2, OPN and BMP2 were both decreased in 3-MA group, compared to GlcN group. ALP is one of the phenotypic markers of osteoblasts, which directly reflects the activity or function of osteoblasts, and is also the best indicator for evaluating bone mineralization disorders in the body [ 60 ]. ALP staining showed that the number of osteoblasts was decreased in 3-MA group, compared to GlcN group.…”

Section: Discussionmentioning

confidence: 99%

Glucosamine delays the progression of osteoporosis in senile mice by promoting osteoblast autophagy

Huang

Zheng

et al. 2022

Nutr Metab (Lond)

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Background Senile osteoporosis (SOP) is one of the most prevalent diseases that afflict the elderly population, which characterized by decreased osteogenic ability. Glucosamine (GlcN) is an over-the-counter dietary supplement. Our previous study reported that GlcN promotes osteoblast proliferation by activating autophagy in vitro. The purpose of this study is to determine the effects and mechanisms of GlcN on senile osteoporosis and osteogenic differentiation in vivo. Methods Aging was induced by subcutaneous injection of d-Galactose (d-Gal), and treated with GlcN or vehicle. The anti-senile-osteoporosis effect of GlcN was explored by examining changes in micro-CT, serum indicators, body weight, protein and gene expression of aging and apoptosis. Additionally, the effects of GlcN on protein and gene expression of osteogenesis and autophagy were observed by inhibiting autophagy with 3-methyladenine (3-MA). Results GlcN significantly improved bone mineral density (BMD) and bone micro-architecture, decreased skeletal senescence and apoptosis and increased osteogenesis in d-Gal induced osteoporotic mice. While all effect was reversed with 3-MA. Conclusion GlcN effectively delayed the progression of osteoporosis in senile osteoporotic mice by promoting osteoblast autophagy. This study suggested that GlcN may be a prospective candidate drug for the treatment of SOP.

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Lung tumor cells inhibit bone mineralization and osteoblast activity

Cited by 10 publications

References 40 publications

Selection of lncRNAs That Influence the Prognosis of Osteosarcoma Based on Copy Number Variation Data

Selection of lncRNAs That Influence the Prognosis of Osteosarcoma Based on Copy Number Variation Data

Bone mineral density as an individual prognostic biomarker in NSCLC patients treated with immune checkpoint inhibitors

Glucosamine delays the progression of osteoporosis in senile mice by promoting osteoblast autophagy

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