Primary tumor genotype is an important determinant in identification of lung cancer propagating cells.
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.
Curtis
Stephen J
SJ
Stem Cell Program, Children's Hospital Boston, Boston, MA 02115, USA.
Sinkevicius
Kerstin W
KW
Li
Danan
D
Lau
Allison N
AN
Roach
Rebecca R
RR
Zamponi
Raffaella
R
Woolfenden
Amber E
AE
Kirsch
David G
DG
Wong
Kwok-Kin
KK
Kim
Carla F
CF
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