Tumor oncogenotypes and lung cancer stem cell identity

Abstract

In this issue of Cell Stem Cell, Curtis et. al. (2010) reveal that the identities of lung cancer stem cell populations differ depending on the specific tumor oncogenotype in three murine lung adenocarcinoma models. These findings highlight the importance of determining the cancer stem cell oncogenotype for genotypically diverse malignancies.

Figure 1. Tumor Propagating Capacity of Sca-1⁺ Lung Cancer Cells

Transgenic mice harboring mutant Kras (left), mutant Kras with a p53 deficiency (center) or mutant EGFR (right) all develop lung adenocarcinomas that harbor a similar proportion of cells expressing the mouse stem cell (and BASC) marker Sca-1 (blue cells). The tumor propagating capacity (TPC) of Sca-1⁺ and Sca-1⁻ cells from each primary tumor genotype was tested by implanting small numbers of sorted cells into the lungs of recipient mice. When isolated from primary Kras tumors, both Sca-1⁺ and Sca-1⁻ cells generated secondary tumors that recapitulated the Sca-1 cell heterogeneity found in the primary tumor (left). However, in tumors with mutant Kras and p53 deficiency, Sca-1⁺ cells possessed a greater capacity for secondary tumor formation (represented as a larger tumor) than Sca-1⁻ cells (center). In addition, secondary tumors derived from Sca-1⁺ cells possessed a similar proportion of Sca-1⁺ cells observed in the primary tumor, whereas the few small tumors derived from Sca-1⁻ cells did not have a detectable Sca-1⁺ population. These data would suggest Sca-1⁺ cells in this tumor genotype are enriched in lung cancer stem cells. The opposite appears to be true in mutant EGFR adenocarcinomas, in which Sca-1⁻ cells exhibited a greater capacity for generating secondary tumors (right). The distribution of Sca-1⁺ cells in secondary mutant EGFR tumors was not determined.