Journal
CELL STEM CELL
Volume 7, Issue 1, Pages 127-133Publisher
CELL PRESS
DOI: 10.1016/j.stem.2010.05.021
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Funding
- DoD, Air Force Office of Scientific Research [32 CFR 168a]
- American Cancer Society [PF-09-121-01-DDC]
- Dana Farber Harvard Cancer Center Lung Cancer [P50 CA090578, R01 AG2400401, R01 CA122794, R01 CA140594]
- V Foundation, American Cancer Society [RSG-08-082-01-MGO]
- Harvard Stem Cell Institute
- NIH/NCI [2P50CA090578]
- Lung Cancer Alliance
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Successful cancer therapy requires the elimination or incapacitation of all tumor cells capable of regenerating a tumor. Therapeutic advances therefore necessitate the characterization of the cells that are able to propagate a tumor in vivo. We show an important link between tumor genotype and isolation of tumor-propagating cells (TPCs). Three mouse models of the most common form of human lung cancer each had TPCs with a unique cell-surface phenotype. The cell-surface marker Sca1 did not enrich for TPCs in tumors initiated with oncogenic Kras, and only Sca1-negative cells propagated EGFR mutant tumors. In contrast, Sca1-positive cells were enriched for tumor-propagating activity in Kras tumors with p53 deficiency. Primary tumors that differ in genotype at just one locus can therefore have tumor-propagating cell populations with distinct markers. Our studies show that the genotype of tumor samples must be considered in studies to identify, characterize, and target tumor-propagating cells.
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