A Humanized Cancer-Bone Metastasis Mouse Model Based on Silica Nanoparticles-Incorporated Human Demineralized Bone Matrix

2019 ◽  
Vol 15 (12) ◽  
pp. 2363-2375 ◽  
Author(s):  
Genlan Ye ◽  
Chuangkun Li ◽  
Xiaoliang Zhao ◽  
Feng Wen ◽  
Leyu Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Mouse Model ◽  
Cancer Cells ◽  
Bone Tissue ◽  
Drug Screening ◽  
Human Cancer ◽  
Demineralized Bone Matrix ◽  
Bone Matrix ◽  
Bone Microenvironment

Breast cancer tends to spread to other organs and bone metastasis has the highest frequency in breast cancer metastasis, while its mechanisms are not clear and the current treatments are not very effective. To better study the mechanisms and facilitate drug screening for breast cancer bone metastasis, an in vivo mouse model needs to be constructed. However, the construction of the humanized mouse model for cancer bone metastasis which will mimick real interactions between cancer tissue and bone tissue in the human microenvironment remains a challenge. In this study, we constructed a human engineering bone tissue composed with the human osteoblast-like cells (SaOS-2 cells) and the silica nanoparticlesincorporated human demineralized bone matrix (Si/DBM). The engineered bone was then transplanted into a nude mouse to build a humanized bone microenvironment. The human breast cancer cells were then injected into the fat pads of the nude mouse to form an orthotopic tumor. The results showed that the engineered bone tissue-constructed humanized bone microenvironment had significant advantages when inducing human cancer cells to metastasize into the engineered bone tissue. Further, the SaOS-2/Si/DBM had a stronger ability to entice cancer-bone metastasis through promoting osteogenesis compared to the SaOS-2/DBM. Accordingly, this study highlights a novel, facile and effective mouse model for human cancer-bone metastasis, which will provide a platform to explore the mechanisms and anti-tumor drug screening for cancer-bone metastasis.

scholarly journals Ipriflavone inhibits osteolytic bone metastasis of human breast cancer cells in a nude mouse model

2002 ◽  
Vol 100 (4) ◽  
pp. 381-387 ◽  
Author(s):  
Teruo Iwasaki ◽  
Mutsuko Mukai ◽  
Tohru Tsujimura ◽  
Masaharu Tatsuta ◽  
Hiroyuki Nakamura ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Mouse Model ◽  
Cancer Cells ◽  
Nude Mouse ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Nude Mouse Model

Biological and Toxicological Evaluation of N-(4methyl-phenyl)-4-methylphthalimide on Bone Cancer in Mice

2019 ◽  
Vol 19 (5) ◽  
pp. 667-676
Author(s):  
José R. Santin ◽  
Gislaine F. da Silva ◽  
Maria V.D. Pastor ◽  
Milena F. Broering ◽  
Roberta Nunes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
In Silico ◽  
Bone Matrix ◽  
Micronucleus Assay ◽  
Repeated Treatment ◽  
Toxicological Evaluation ◽  
Toxicological Analysis ◽  
Breast Cancer Bone Metastasis

Background: It was recently demonstrated that the phthalimide N-(4-methyl-phenyl)-4- methylphthalimide (MPMPH-1) has important effects against acute and chronic pain in mice, with a mechanism of action correlated to adenylyl cyclase inhibition. Furthermore, it was also demonstrated that phthalimide derivatives presented antiproliferative and anti-tumor effects. Considering the literature data, the present study evaluated the effects of MPMPH-1 on breast cancer bone metastasis and correlated painful symptom, and provided additional toxicological information about the compound and its possible metabolites. Methods: In silico toxicological analysis was supported by in vitro and in vivo experiments to demonstrate the anti-tumor and anti-hypersensitivity effects of the compound. Results: The data obtained with the in silico toxicological analysis demonstrated that MPMPH-1 has mutagenic potential, with a low to moderate level of confidence. The mutagenicity potential was in vivo confirmed by micronucleus assay. MPMPH-1 treatments in the breast cancer bone metastasis model were able to prevent the osteoclastic resorption of bone matrix. Regarding cartilage, degradation was considerably reduced within the zoledronic acid group, while in MPMPH-1, chondrocyte multiplication was observed in random areas, suggesting bone regeneration. Additionally, the repeated treatment of mice with MPMPH-1 (10 mg/kg, i.p.), once a day for up to 36 days, significantly reduces the hypersensitivity in animals with breast cancer bone metastasis. Conclusion: Together, the data herein obtained show that MPMPH-1 is relatively safe, and significantly control the cancer growth, allied to the reduction in bone reabsorption and stimulation of bone and cartilage regeneration. MPMPH-1 effects may be linked, at least in part, to the ability of the compound to interfere with adenylylcyclase pathway activation.

scholarly journals Arginine Methyltransferase PRMT1 Regulates p53 Activity in Breast Cancer

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 789
Author(s):  
Li-Ming Liu ◽  
Qiang Tang ◽  
Xin Hu ◽  
Jing-Jing Zhao ◽  
Yuan Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Asymmetric Dimethylarginine ◽  
Human Cancer ◽  
Specific Inhibitor ◽  
Dependent Manner ◽  
Breast Tumorigenesis ◽  
Stress Signals

The protein p53 is one of the most important tumor suppressors, responding to a variety of stress signals. Mutations in p53 occur in about half of human cancer cases, and dysregulation of the p53 function by epigenetic modifiers and modifications is prevalent in a large proportion of the remainder. PRMT1 is the main enzyme responsible for the generation of asymmetric-dimethylarginine, whose upregulation or aberrant splicing has been observed in many types of malignancies. Here, we demonstrate that p53 function is regulated by PRMT1 in breast cancer cells. PRMT1 knockdown activated the p53 signal pathway and induced cell growth-arrest and senescence. PRMT1 could directly bind to p53 and inhibit the transcriptional activity of p53 in an enzymatically dependent manner, resulting in a decrease in the expression levels of several key downstream targets of the p53 pathway. We were able to detect p53 asymmetric-dimethylarginine signals in breast cancer cells and breast cancer tissues from patients, and the signals could be significantly weakened by silencing of PRMT1 with shRNA, or inhibiting PRMT1 activity with a specific inhibitor. Furthermore, PRMT1 inhibitors significantly impeded cell growth and promoted cellular senescence in breast cancer cells and primary tumor cells. These results indicate an important role of PRMT1 in the regulation of p53 function in breast tumorigenesis.

scholarly journals A novel gelatin/chitooligosaccharide/demineralized bone matrix composite scaffold and periosteum-derived mesenchymal stem cells for bone tissue engineering

2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Thakoon Thitiset ◽  
Siriporn Damrongsakkul ◽  
Supansa Yodmuang ◽  
Wilairat Leeanansaksiri ◽  
Jirun Apinun ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Demineralized Bone Matrix ◽  
Bone Matrix ◽  
Alp Activity

Abstract Background A novel biodegradable scaffold including gelatin (G), chitooligosaccharide (COS), and demineralized bone matrix (DBM) could play a significant part in bone tissue engineering. The present study aimed to investigate the biological characteristics of composite scaffolds in combination of G, COS, and DBM for in vitro cell culture and in vivo animal bioassays. Methods Three-dimensional scaffolds from the mixture of G, COS, and DBM were fabricated into 3 groups, namely, G, GC, and GCD using a lyophilization technique. The scaffolds were cultured with mesenchymal stem cells (MSCs) for 4 weeks to determine biological responses such as cell attachment and cell proliferation, alkaline phosphatase (ALP) activity, calcium deposition, cell morphology, and cell surface elemental composition. For the in vivo bioassay, G, GC, and GCD, acellular scaffolds were implanted subcutaneously in 8-week-old male Wistar rats for 4 weeks and 8 weeks. The explants were assessed for new bone formation using hematoxylin and eosin (H&E) staining and von Kossa staining. Results The MSCs could attach and proliferate on all three groups of scaffolds. Interestingly, the ALP activity of MSCs reached the greatest value on day 7 after cultured on the scaffolds, whereas the calcium assay displayed the highest level of calcium in MSCs on day 28. Furthermore, weight percentages of calcium and phosphorus on the surface of MSCs after cultivation on the GCD scaffolds increased when compared to those on other scaffolds. The scanning electron microscopy images showed that MSCs attached and proliferated on the scaffold surface thoroughly over the cultivation time. Mineral crystal aggregation was evident in GC and greatly in GCD scaffolds. H&E staining illustrated that G, GC, and GCD scaffolds displayed osteoid after 4 weeks of implantation and von Kossa staining confirmed the mineralization at 8 weeks in G, GC, and GCD scaffolds. Conclusion The MSCs cultured in GCD scaffolds revealed greater osteogenic differentiation than those cultured in G and GC scaffolds. Additionally, the G, GC, and GCD scaffolds could promote in vivo ectopic bone formation in rat model. The GCD scaffolds exhibited maximum osteoinductive capability compared with others and may be potentially used for bone regeneration.

Silencing of Irf7 pathways in breast cancer cells promotes bone metastasis through immune escape

2012 ◽  
Vol 18 (8) ◽  
pp. 1224-1231 ◽  
Author(s):  
Bradley N Bidwell ◽  
Clare Y Slaney ◽  
Nimali P Withana ◽  
Sam Forster ◽  
Yuan Cao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Immune Escape

scholarly journals MicroRNA let-7g directly targets forkhead box C2 (FOXC2) to modulate bone metastasis in breast cancer

Open Medicine ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. 157-162 ◽  
Author(s):  
Lei Wang ◽  
Ming Li ◽  
Yongxin Zhou ◽  
Yu Zhao
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Bone Metastasis ◽  
Western Blot ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Qrt Pcr ◽  
Forkhead Box ◽  
Novel Target ◽  
Cancer Tissues

AbstractAberrantly expressed microRNAs have been implicated in lots of cancers. Reduced amounts of let-7g have been found in breast cancer tissues. The function of let-7g in bone metastasis of breast cancer remains poorly understood. This study is to explore the significance of let-7g and its novel target gene in bone metastasis of breast cancer.The expression of let-7g or forkhead box C2 (FOXC2) was measured in human clinical breast cancer tissues with bone metastasis by using quantitative real-time Polymerase Chain Reaction (qRT-PCR). After transfection with let-7g or anti-let-7g in breast cancer cell linesMDA-MB-231or SK-BR3, qRT-PCR and Western blot were done to test the levels of let-7g and FOXC2. The effect of anti-let-7g and/ or FOXC2 RNA interference (RNAi) on cell migration in breast cancer cells was evaluated by using wound healing assay.Clinically, qRT-PCR showed that FOXC2 levels were higher in breast cancer tissues with bone metastasis than those in their noncancerous counterparts. Let-7g was showed to be negatively correlated with FOXC2 in human breast cancer samples with bone metastasis. We found that enforced expression of let-7g reduced levels of FOXC2 protein by using Western blot in MDA-MB-231 cells. Conversely, anti-let-7g enhanced levels of FOXC2 in SK-BR3 cells. In terms of function, anti-let-7g accelerated migration of SK-BR3 cells. Interestingly, FOXC2 RNAi abrogated anti-let-7g-mediated migration in breast cancer cells. Thus, we conclude that let-7g suppresses cell migration through targeting FOXC2 in breast cancer. Our finding provides a new perspective for understanding the mechanism of bone metastasis in breast cancer.

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