Oncogenic transformation of normal breast epithelial cells co-cultured with cancer cells

The heterogeneity in human breast cancer poses a challenge for effective treatment. Better understanding of tumor initiation and development will help to resolve this problem. Current models explaining intratumoral diversity include cancer stem cells, clonal evolution and cancer cell dedifferentiation and reprogramming. Herein, a new model, cancer transmission, is proposed to explain cancer heterogeneity. We found breast cancer cells (MCF10A.NeuT) were capable of transforming normal mammary epithelial cells (MCF10A). The transformed cells exhibited cancerous properties including enhanced proliferation and migration, loss of apical-basal polarity and depolarized acini structure associated with epithelial-mesenchymal transition (EMT). The transformed MCF10A cells displayed distinct EMT characteristics compared to parental cells. We further showed that cancer cell-secreted factors were sufficient to induce cancerous transformation of normal cells. Furthermore, transformed cells were resistant to radiation treatment, providing new insights into mechanisms underlying therapeutic resistance.