title: Evidence for the transmission of neoplastic properties from transformed to normal human stem cells.
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.
authors.affiliation: McMaster Stem Cell and Cancer Research Institute, Michael G. Degroote School of Medicine, Department of Biochemistry, McMaster University, Hamilton, Ontario, Canada.
authors.forename: T E
authors.initials: TE
authors.lastname: Werbowetski-Ogilvie
authors.forename: A
authors.initials: A
authors.lastname: Schnerch
authors.forename: S
authors.initials: S
authors.lastname: Rampalli
authors.forename: C E
authors.initials: CE
authors.lastname: Mills
authors.forename: J B
authors.initials: JB
authors.lastname: Lee
authors.forename: S-H
authors.initials: SH
authors.lastname: Hong
authors.forename: M
authors.initials: M
authors.lastname: Levadoux-Martin
authors.forename: M
authors.initials: M
authors.lastname: Bhatia
mesh_terms: D002450:Cell Communication; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D018920:Coculture Techniques; D053595:Embryonic Stem Cells / Q000473:pathology; D015870:Gene Expression; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D014411:Neoplastic Stem Cells / Q000473:pathology*; D039904:Pluripotent Stem Cells / Q000473:pathology