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

  • Werbowetski-Ogilvie T
  • Schnerch A
  • Rampalli S
 et al. 
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Abstract

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.

Author-supplied keywords

  • differentiation
  • human stem cells
  • selfrenewal
  • transformation

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Authors

  • T. E. Werbowetski-Ogilvie

  • A. Schnerch

  • S. Rampalli

  • C. E. Mills

  • J. B. Lee

  • S. H. Hong

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