Evidence for the transmission of neoplastic properties from transformed to normal human stem cells

The in vivo relationship between human tumor cells and interacting normal cells in their local environment is poorly understood. Here, using a uniquely developed in vitro co-culture system for human embryonic stem cells (hESCs), we examined the interactions between transformed and normal human stem cells. Co-culture of transformed-hESCs (t-hESCs) with normal hESCs led to enhanced self-renewal and niche independence in normal hESCs. Global gene expression analysis of normal hESCs after timed exposure to t-hESCs indicated a transition of the molecular network controlling the hESC state, which included epigenetic changes, towards neoplastic features. These included enhanced pluripotent marker expression and a differentiation blockade as major hallmark changes. Functional studies revealed a loss in normal terminal differentiation programs for both hematopoiesis and neural lineages after normal stem cell co-culture with transformed variants. This transmission of neoplastic properties from t-hESCs to normal hESCs was dependent on direct cell-cell contact. Our study indicates that normal human stem cells can co-opt neoplastic cancer stem cell properties, raising the possibility that assimilation of healthy cells towards neoplastic behavior maybe a contributing feature of sustained tumorigenesis in vivo.