Primary Tumor Genotype is an Important Determinant in Identification of Lung Cancer Propagating Cells

Overview

Journal Cell Stem Cell

Publisher Cell Press

Specialty Cell Biology

Date 2010 Jul 13

PMID 20621056

Citations 77

Authors

Stephen J Curtis

Kerstin W Sinkevicius

Danan Li

Allison N Lau

Rebecca R Roach

Raffaella Zamponi

Amber E Woolfenden

David G Kirsch

Kwok-Kin Wong

Carla F Kim

Affiliations

Soon will be listed here.

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.

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