Spontaneous Fusion With, and Transformation of Mouse Stroma By, Malignant Human Breast Cancer Epithelium

Adenocarcinoma cells from the pleural effusion of a patient with breast cancer were injected into the mammary glands of nude mice and grown into solid tumors. A cell line derived from these tumors expressed alpha-smooth muscle actin but not human cytokeratin 7, indicating "activated" stroma of mouse origin. Cells in mitosis exhibited mainly polyploid mouse karyotypes, but 30% had mixed mouse and human chromosomes, among which 8% carried mouse/human translocations. Nuclei of interphase cells were 64% hybrid. Hybrid mouse/human nuclei were also detected in the primary xenograft. Thus, synkaryons formed in the solid tumor by spontaneous fusion between the malignant human epithelium and the surrounding normal host mouse stroma. The transformed stroma-derived cells are tumorigenic with histopathologic features of malignancy, suggesting a new mechanism for tumor progression.