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Curtis, Stephen J.; Sinkevicius, Kerstin W.; Li, Danan; Lau, Allison N.; Roach, Rebecca R.; Zamponi, Raffaella; Woolfenden, Amber E.; Kirsch, David G.; Wong, Kwok-Kin; Kim, Carla F.
Cell stem cell, 07/2010, Volume: 7, Issue: 1Journal Article
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. Display omitted ► Identification of the first lung tumor-propagating cell population ► Lung cancers of different genotype have tumor-propagating cells with distinct markers ► Tumor samples should be separated by genotype to study tumor-propagating cells
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