Expression profiling of CD24+ and CD24- tumor cells in Kras-driven NSCLC mouse model

Sustained tumor progression has been attributed to a distinct population of tumor-propagating cells (TPCs). To identify TPCs relevant to lung cancer pathogenesis, we investigated functional heterogeneity in tumor cells isolated from Kras-driven mouse models of non-small cell lung cancer (NSCLC). CD24+ITGB4+Notchhi cells are capable of propagating tumor growth in both a clonogenic and an orthotopic serial transplantation assay. While all four Notch receptors mark TPCs, Notch3 plays a non-redundant role in tumor cell propagation in two mouse model and in human NSCLC. The TPC population is enriched after chemotherapy and the gene signature of mouse TPCs correlates with poor prognosis in human NSCLC. The unique role of Notch3 in tumor propagation may provide a therapeutic target for NSCLC Highly purified primary tumor cells were FACS sorted based on expression of CD24. Samples were derived from six mice.