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

Abstract

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.