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A tissue-engineered humanized xenograft model of human breast cancer metastasis to bone.

Disease models & mechanisms (2014-04-10)
Laure Thibaudeau, Anna V Taubenberger, Boris M Holzapfel, Verena M Quent, Tobias Fuehrmann, Parisa Hesami, Toby D Brown, Paul D Dalton, Carl A Power, Brett G Hollier, Dietmar W Hutmacher
RESUMO

The skeleton is a preferred homing site for breast cancer metastasis. To date, treatment options for patients with bone metastases are mostly palliative and the disease is still incurable. Indeed, key mechanisms involved in breast cancer osteotropism are still only partially understood due to the lack of suitable animal models to mimic metastasis of human tumor cells to a human bone microenvironment. In the presented study, we investigate the use of a human tissue-engineered bone construct to develop a humanized xenograft model of breast cancer-induced bone metastasis in a murine host. Primary human osteoblastic cell-seeded melt electrospun scaffolds in combination with recombinant human bone morphogenetic protein 7 were implanted subcutaneously in non-obese diabetic/severe combined immunodeficient mice. The tissue-engineered constructs led to the formation of a morphologically intact 'organ' bone incorporating a high amount of mineralized tissue, live osteocytes and bone marrow spaces. The newly formed bone was largely humanized, as indicated by the incorporation of human bone cells and human-derived matrix proteins. After intracardiac injection, the dissemination of luciferase-expressing human breast cancer cell lines to the humanized bone ossicles was detected by bioluminescent imaging. Histological analysis revealed the presence of metastases with clear osteolysis in the newly formed bone. Thus, human tissue-engineered bone constructs can be applied efficiently as a target tissue for human breast cancer cells injected into the blood circulation and replicate the osteolytic phenotype associated with breast cancer-induced bone lesions. In conclusion, we have developed an appropriate model for investigation of species-specific mechanisms of human breast cancer-related bone metastasis in vivo.

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Fosfato de sódio, ACS reagent, ≥99.0%
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Acetato de sódio, anhydrous, ReagentPlus®, ≥99.0%
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Dexametasona, powder, BioReagent, suitable for cell culture, ≥97%
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Acetato de sódio, ACS reagent, ≥99.0%
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Fosfato de sódio, puriss. p.a., ACS reagent, anhydrous, ≥99.0% (T)
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Acetato de sódio, puriss. p.a., ACS reagent, reag. Ph. Eur., anhydrous
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Hidrocortisona, BioReagent, suitable for cell culture
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Iodeto de propídio, ≥94.0% (HPLC)
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Hidrocortisona, γ-irradiated, powder, BioXtra, suitable for cell culture
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Fosfato de sódio, puriss., meets analytical specification of Ph. Eur., BP, USP, FCC, E 339, anhydrous, 98-100.5% (calc. to the dried substance)
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Dexametasona, ≥98% (HPLC), powder
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Hidrocortisona, ≥98% (HPLC)
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Fosfato de sódio, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥99.0%
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Fosfato de sódio, for molecular biology, ≥98.5% (titration)
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Peróxido de hidrogênio, contains ~200 ppm acetanilide as stabilizer, 3 wt. % in H2O
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Fluorescein diacetate, used as cell viability stain
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Sodium phosphate dibasic solution, BioUltra, 0.5 M in H2O
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Hematoxilina
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Peróxido de hidrogênio, purum p.a., ≥35% (RT)
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Potassium, chunks (in mineral oil), 98% trace metals basis
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Acetato de sódio, >99%, FG
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Acetato de sódio, 99.995% trace metals basis
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Potassium hydride, 30 wt % dispersion in mineral oil
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Sodium acetate solution, BioUltra, for molecular biology, ~3 M in H2O
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Acetato de sódio, anhydrous, BioUltra, for luminescence, for molecular biology, ≥99.0% (NT)
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Dexametasona, powder, γ-irradiated, BioXtra, suitable for cell culture, ≥80% (HPLC)
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Fosfato de sódio, 99.95% trace metals basis
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Acetato de sódio, anhydrous, free-flowing, Redi-Dri, ACS reagent, ≥99.0%
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Acetato de sódio, powder, BioReagent, suitable for electrophoresis, suitable for cell culture, suitable for insect cell culture, ≥99%
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Fosfato de sódio, BioUltra, for molecular biology, ≥99.5% (T)