PMID- 12629218
OWN - NLM
STAT- MEDLINE
DCOM- 20030522
LR  - 20250214
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 100
IP  - 7
DP  - 2003 Apr 1
TI  - Prospective identification of tumorigenic breast cancer cells.
PG  - 3983-8
AB  - Breast cancer is the most common malignancy in United States women, accounting 
      for >40,000 deaths each year. These breast tumors are comprised of phenotypically 
      diverse populations of breast cancer cells. Using a model in which human breast 
      cancer cells were grown in immunocompromised mice, we found that only a minority 
      of breast cancer cells had the ability to form new tumors. We were able to 
      distinguish the tumorigenic (tumor initiating) from the nontumorigenic cancer 
      cells based on cell surface marker expression. We prospectively identified and 
      isolated the tumorigenic cells as CD44(+)CD24(-/low)Lineage(-) in eight of nine 
      patients. As few as 100 cells with this phenotype were able to form tumors in 
      mice, whereas tens of thousands of cells with alternate phenotypes failed to form 
      tumors. The tumorigenic subpopulation could be serially passaged: each time cells 
      within this population generated new tumors containing additional 
      CD44(+)CD24(-/low)Lineage(-) tumorigenic cells as well as the phenotypically 
      diverse mixed populations of nontumorigenic cells present in the initial tumor. 
      The ability to prospectively identify tumorigenic cancer cells will facilitate 
      the elucidation of pathways that regulate their growth and survival. Furthermore, 
      because these cells drive tumor development, strategies designed to target this 
      population may lead to more effective therapies.
FAU - Al-Hajj, Muhammad
AU  - Al-Hajj M
AD  - Department of Internal Medicine, Comprehensive Cancer Center, University of 
      Michigan Medical School, Ann Arbor, MI 48109, USA.
FAU - Wicha, Max S
AU  - Wicha MS
FAU - Benito-Hernandez, Adalberto
AU  - Benito-Hernandez A
FAU - Morrison, Sean J
AU  - Morrison SJ
FAU - Clarke, Michael F
AU  - Clarke MF
LA  - eng
GR  - P01 CA075136/CA/NCI NIH HHS/United States
GR  - P30 CA046592/CA/NCI NIH HHS/United States
GR  - CA-075136/CA/NCI NIH HHS/United States
GR  - CA-46592/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030310
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 (Antigens, CD)
SB  - IM
EIN - Proc Natl Acad Sci U S A. 2003 May 27;100(11):6890
CIN - Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3547-9. doi: 10.1073/pnas.0830967100. 
      PMID: 12657737
CIN - Dis Model Mech. 2010 May-Jun;3(5-6):257-8. doi: 10.1242/dmm.005207. PMID: 
      20427552
MH  - Animals
MH  - Antigens, CD/analysis
MH  - Breast Neoplasms/*pathology
MH  - Female
MH  - Flow Cytometry
MH  - Humans
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Neoplasm Metastasis/*pathology
MH  - Pleural Effusion/physiopathology
MH  - Transplantation, Heterologous/physiology
PMC - PMC153034
EDAT- 2003/03/12 04:00
MHDA- 2003/05/23 05:00
PMCR- 2003/10/01
CRDT- 2003/03/12 04:00
PHST- 2003/03/12 04:00 [pubmed]
PHST- 2003/05/23 05:00 [medline]
PHST- 2003/03/12 04:00 [entrez]
PHST- 2003/10/01 00:00 [pmc-release]
AID - 0530291100 [pii]
AID - 0291 [pii]
AID - 10.1073/pnas.0530291100 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8. doi: 10.1073/pnas.0530291100. 
      Epub 2003 Mar 10.