Primary Tumor Genotype Is an Important Determinant in Identification of Lung Cancer Propagating Cells
Curtis, Stephen J.
Sinkevicius, Kerstin W.
Lau, Allison N.
Roach, Rebecca R.
Woolfenden, Amber E.
Kirsch, David G.
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CitationCurtis, Stephen J., Kerstin W. Sinkevicius, Danan Li, Allison N. Lau, Rebecca R. Roach, Raffaella Zamponi, Amber E. Woolfenden et al. "Primary Tumor Genotype Is an Important Determinant in Identification of Lung Cancer Propagating Cells." Cell Stem Cell 7, no. 1 (2010): 127-133. DOI: 10.1016/j.stem.2010.05.021
AbstractSuccessful 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.
Depending on the tumor initiating genetic event in three tractable mouse models of lung adenocarcinoma, the surface maker Sca1 had variable success in identifying cells with tumor-propagating activity. These findings uncover the impact that tumor genotype can have on the phenotype of tumor-propagating cells, which may have important therapeutic significance.
-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
Citable link to this pagehttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37372578
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