Xenograft-Derived Human Breast Cancer Organoids Can Form Chimeras with Host Mouse Mammary Epithelial Cells Which Promote Tumor Cell Proliferation

Breast cancer progression and treatment responsiveness are significantly influenced by the tumor microenvironment. Therefore, transplantation into the mammary fat pad is widely employed to establish a mouse xenograft model of breast cancer. This study reports chimeric organoids derived from breast cancer xenografts composed of human and mouse cells. During passaging of an organoid line derived from breast cancer xenografts, characteristic cell clusters composed of smaller cells were observed. Immunostaining with a mouse-specific antibody revealed that the smaller cells were mouse cells composed of luminal- and basal-like cells. Chimeric organoids were observed in four of the six xenograft-derived organoid lines. Organoids composed solely of human cells rapidly diminished after passaging, with chimeric and mouse-cell-only organoids becoming predominant. When human breast cancer cells were co-cultured with mouse mammary epithelial cells, chimeras were frequently observed. The PCNA positivity rate in breast cancer cells within chimeras was higher than that in breast cancer cells within organoids composed solely of human cells. These findings indicate that xenograft-derived breast cancer organoids frequently contain mouse cells and that mouse mammary epithelial cells promote the proliferation of human breast cancer cells.