title: Primary tumor genotype is an important determinant in identification of lung cancer propagating cells.
abstract: 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.
authors.affiliation: Stem Cell Program, Children's Hospital Boston, Boston, MA 02115, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Curtis
authors.forename: Kerstin W
authors.initials: KW
authors.lastname: Sinkevicius
authors.forename: Danan
authors.initials: D
authors.lastname: Li
authors.forename: Allison N
authors.initials: AN
authors.lastname: Lau
authors.forename: Rebecca R
authors.initials: RR
authors.lastname: Roach
authors.forename: Raffaella
authors.initials: R
authors.lastname: Zamponi
authors.forename: Amber E
authors.initials: AE
authors.lastname: Woolfenden
authors.forename: David G
authors.initials: DG
authors.lastname: Kirsch
authors.forename: Kwok-Kin
authors.initials: KK
authors.lastname: Wong
authors.forename: Carla F
authors.initials: CF
authors.lastname: Kim
mesh_terms: D000818:Animals; D005434:Flow Cytometry; D005838:Genotype; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D014407:Tumor Cells, Cultured