title: Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state.
abstract: Current models of stem cell biology assume that normal and neoplastic stem cells reside at the apices of hierarchies and differentiate into nonstem progeny in a unidirectional manner. Here we identify a subpopulation of basal-like human mammary epithelial cells that departs from that assumption, spontaneously dedifferentiating into stem-like cells. Moreover, oncogenic transformation enhances the spontaneous conversion, so that nonstem cancer cells give rise to cancer stem cell (CSC)-like cells in vitro and in vivo. We further show that the differentiation state of normal cells-of-origin is a strong determinant of posttransformation behavior. These findings demonstrate that normal and CSC-like cells can arise de novo from more differentiated cell types and that hierarchical models of mammary stem cell biology should encompass bidirectional interconversions between stem and nonstem compartments. The observed plasticity may allow derivation of patient-specific adult stem cells without genetic manipulation and holds important implications for therapeutic strategies to eradicate cancer.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Chaffer
authors.forename: Ines
authors.initials: I
authors.lastname: Brueckmann
authors.forename: Christina
authors.initials: C
authors.lastname: Scheel
authors.forename: Alicia J
authors.initials: AJ
authors.lastname: Kaestli
authors.forename: Paul A
authors.initials: PA
authors.lastname: Wiggins
authors.forename: Leonardo O
authors.initials: LO
authors.lastname: Rodrigues
authors.forename: Mary
authors.initials: M
authors.lastname: Brooks
authors.forename: Ferenc
authors.initials: F
authors.lastname: Reinhardt
authors.forename: Ying
authors.initials: Y
authors.lastname: Su
authors.forename: Kornelia
authors.initials: K
authors.lastname: Polyak
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Arendt
authors.forename: Charlotte
authors.initials: C
authors.lastname: Kuperwasser
authors.forename: Brian
authors.initials: B
authors.lastname: Bierie
authors.forename: Robert A
authors.initials: RA
authors.lastname: Weinberg
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000502:physiology; D000818:Animals; D001940:Breast / Q000166:cytology* / Q000502:physiology; D001943:Breast Neoplasms / Q000473:pathology* / Q000503:physiopathology; D051927:CD24 Antigen / Q000378:metabolism; D054337:Cell Dedifferentiation / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000166:cytology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000473:pathology / Q000502:physiology; D033581:Stem Cell Transplantation; D014183:Transplantation, Heterologous
chemical_list: D051927:CD24 Antigen; C497889:CD24 protein, human; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D008565:Membrane Proteins; C106354:flotillins