A brain metastasis model for breast cancer using human embryonic stem cell-derived cerebral organoids

Abstract

Background Breast cancer is a common cause of brain metastasis. Although breast cancer has relatively high survival rates, its survival rate after metastasis to the brain is lower. Conventional two-dimensional cell culture models and animal models are widely used in metastatic cancer research, and these models have tremendously contributed to the understanding of this disease. However, these models have some limitations, such as different physiological features and genetic backgrounds. Methods We established a simple metastatic breast cancer model using human pluripotent stem cell-derived cerebral organoids (COs)—in this case, breast cancer cerebral organoids (BC-COs). Results Using the BC-CO model, we induced the metastasis of MDA-MB-231 cells into COs by co-culture of cells with COs and compared the differences between adapted cancer cells in BC-COs and non-adapted cells. Our results showed that the proliferative capacity increased in adapted cells. Additionally, the expression levels of endothelial-mesenchymal transition markers and cancer stem cells were significantly higher in adapted cancer cells. Conclusion We conclude that metastasis promotes the metastatic capacity of breast cancer cells. Our results also showed that the BC-CO model could be a novel tool for research on brain metastasis in breast cancer.

Keywords

• organoids
• breast neoplasm
• neoplasm metastasis
• adaptation