A Humanized Cancer-Bone Metastasis Mouse Model Based on Silica Nanoparticles-Incorporated Human Demineralized Bone Matrix.
A Humanized Cancer-Bone Metastasis Mouse Model Based on Silica Nanoparticles-Incorporated Human Demineralized Bone Matrix.
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DOI：
10.1166/jbn.2019.2860
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发表时间：
2019-12
影响因子：
2.9
通讯作者：
Genlan Ye;Chuangkun Li;X. Zhao;Feng Wen;Leyu Wang;Xiaozhong Qiu
中科院分区：
文献类型：
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作者：
Genlan Ye;Chuangkun Li;X. Zhao;Feng Wen;Leyu Wang;Xiaozhong Qiu
乳腺癌易向其他器官扩散，骨转移在乳腺癌转移中发生率最高，但其机制尚不清楚，目前的治疗方法也不是很有效。为了更好地研究乳腺癌骨转移的机制和促进药物筛选，需要建立一种体内小鼠模型。然而，构建人源化的癌症骨转移小鼠模型，其将模拟人类微环境中癌组织和骨组织之间的真实的相互作用，仍然是一个挑战。本研究以人成骨样细胞（SaOS-2细胞）和二氧化硅纳米颗粒复合的人脱钙骨基质（Si/DBM）为复合材料，构建了人工程骨组织。然后将该工程骨移植到裸鼠体内，以构建人源化骨微环境。然后将人乳腺癌细胞注射到裸鼠的脂肪垫中以形成原位肿瘤。结果表明，工程化骨组织构建的人源化骨微环境在诱导人癌细胞向工程化骨组织转移时具有显著优势。此外，与SaOS-2/DBM相比，SaOS-2/Si/DBM具有更强的通过促进成骨诱导癌骨转移的能力。因此，本研究建立了一种新型、简便、有效的肿瘤骨转移小鼠模型，为探讨肿瘤骨转移的机制和抗肿瘤药物筛选提供了平台。
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.