PMID- 18765800
OWN - NLM
STAT- MEDLINE
DCOM- 20080930
LR  - 20220309
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 105
IP  - 36
DP  - 2008 Sep 9
TI  - Single-cell cloning of colon cancer stem cells reveals a multi-lineage 
      differentiation capacity.
PG  - 13427-32
LID - 10.1073/pnas.0805706105 [doi]
AB  - Colon carcinoma is one of the leading causes of death from cancer and is 
      characterized by a heterogenic pool of cells with distinct differentiation 
      patterns. Recently, it was reported that a population of undifferentiated cells 
      from a primary tumor, so-called cancer stem cells (CSC), can reconstitute the 
      original tumor on xenotransplantation. Here, we show that spheroid cultures of 
      these colon CSCs contain expression of CD133, CD166, CD44, CD29, CD24, Lgr5, and 
      nuclear beta-catenin, which have all been suggested to mark the (cancer) stem 
      cell population. More importantly, by using these spheroid cultures or freshly 
      isolated tumor cells from multiple colon carcinomas, we now provide compelling 
      evidence to indicate that the capacity to propagate a tumor with all 
      differentiated progeny resides in a single CSC. Single-cell-cloned CSCs can form 
      an adenocarcinoma on xenotransplantation but do not generate the stroma within 
      these tumors. Moreover, they can self-renew and are capable of multilineage 
      differentiation. Further analysis indicated that the lineage decision is dictated 
      by phosphoinositide 3-kinase (PI3K) signaling in CSCs. These data support the 
      hypothesis that tumor hierarchy can be traced back to a single CSC that contains 
      multilineage differentiation capacity, and provides clues to the regulation of 
      differentiation in colon cancers in vivo.
FAU - Vermeulen, L
AU  - Vermeulen L
AD  - Laboratory for Experimental Oncology and Radiobiology, Center for Experimental 
      Molecular Medicine, Academic Medical Center, Meibergdreef 9 1105 AZ, Amsterdam, 
      The Netherlands.
FAU - Todaro, M
AU  - Todaro M
FAU - de Sousa Mello, F
AU  - de Sousa Mello F
FAU - Sprick, M R
AU  - Sprick MR
FAU - Kemper, K
AU  - Kemper K
FAU - Perez Alea, M
AU  - Perez Alea M
FAU - Richel, D J
AU  - Richel DJ
FAU - Stassi, G
AU  - Stassi G
FAU - Medema, J P
AU  - Medema JP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080902
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 (Biomarkers, Tumor)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
SB  - IM
MH  - Adenocarcinoma/metabolism/pathology
MH  - Biomarkers, Tumor/metabolism
MH  - *Cell Differentiation/drug effects
MH  - *Cell Lineage
MH  - Cell Separation/*methods
MH  - Colonic Neoplasms/*pathology
MH  - Humans
MH  - Neoplastic Stem Cells/metabolism/*pathology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Tissue Culture Techniques
PMC - PMC2533206
COIS- The authors declare no conflict of interest.
EDAT- 2008/09/04 09:00
MHDA- 2008/10/01 09:00
PMCR- 2009/03/09
CRDT- 2008/09/04 09:00
PHST- 2008/09/04 09:00 [pubmed]
PHST- 2008/10/01 09:00 [medline]
PHST- 2008/09/04 09:00 [entrez]
PHST- 2009/03/09 00:00 [pmc-release]
AID - 0805706105 [pii]
AID - 4699 [pii]
AID - 10.1073/pnas.0805706105 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13427-32. doi: 
      10.1073/pnas.0805706105. Epub 2008 Sep 2.