PMID- 21498687
OWN - NLM
STAT- MEDLINE
DCOM- 20110715
LR  - 20240109
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 108
IP  - 19
DP  - 2011 May 10
TI  - Normal and neoplastic nonstem cells can spontaneously convert to a stem-like 
      state.
PG  - 7950-5
LID - 10.1073/pnas.1102454108 [doi]
AB  - 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.
FAU - Chaffer, Christine L
AU  - Chaffer CL
AD  - Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
FAU - Brueckmann, Ines
AU  - Brueckmann I
FAU - Scheel, Christina
AU  - Scheel C
FAU - Kaestli, Alicia J
AU  - Kaestli AJ
FAU - Wiggins, Paul A
AU  - Wiggins PA
FAU - Rodrigues, Leonardo O
AU  - Rodrigues LO
FAU - Brooks, Mary
AU  - Brooks M
FAU - Reinhardt, Ferenc
AU  - Reinhardt F
FAU - Su, Ying
AU  - Su Y
FAU - Polyak, Kornelia
AU  - Polyak K
FAU - Arendt, Lisa M
AU  - Arendt LM
FAU - Kuperwasser, Charlotte
AU  - Kuperwasser C
FAU - Bierie, Brian
AU  - Bierie B
FAU - Weinberg, Robert A
AU  - Weinberg RA
LA  - eng
GR  - U54 CA126515/CA/NCI NIH HHS/United States
GR  - U54 CA12515/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20110415
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (CD24 Antigen)
RN  - 0 (CD24 protein, human)
RN  - 0 (CD44 protein, human)
RN  - 0 (Hyaluronan Receptors)
RN  - 0 (Membrane Proteins)
RN  - 0 (flotillins)
SB  - IM
MH  - Adult Stem Cells/cytology/physiology
MH  - Animals
MH  - Breast/*cytology/physiology
MH  - Breast Neoplasms/*pathology/physiopathology
MH  - CD24 Antigen/metabolism
MH  - *Cell Dedifferentiation/physiology
MH  - Cell Transformation, Neoplastic/pathology
MH  - Cells, Cultured
MH  - Epithelial Cells/cytology/physiology
MH  - Female
MH  - Humans
MH  - Hyaluronan Receptors/metabolism
MH  - Mammary Glands, Animal/cytology
MH  - Membrane Proteins/metabolism
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, Nude
MH  - Mice, SCID
MH  - Neoplastic Stem Cells/pathology/physiology
MH  - Stem Cell Transplantation
MH  - Transplantation, Heterologous
PMC - PMC3093533
COIS- The authors declare no conflict of interest.
EDAT- 2011/04/19 06:00
MHDA- 2011/07/16 06:00
PMCR- 2011/11/10
CRDT- 2011/04/19 06:00
PHST- 2011/04/19 06:00 [entrez]
PHST- 2011/04/19 06:00 [pubmed]
PHST- 2011/07/16 06:00 [medline]
PHST- 2011/11/10 00:00 [pmc-release]
AID - 1102454108 [pii]
AID - 201102454 [pii]
AID - 10.1073/pnas.1102454108 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2011 May 10;108(19):7950-5. doi: 
      10.1073/pnas.1102454108. Epub 2011 Apr 15.