A Rare Population of CD24+ITGB4+Notchhi Cells Drives Tumor Propagation in NSCLC and Requires Notch3 for Self-Renewal
Menée à l'aide de deux modèles murins, cette étude met en évidence le rôle joué par une petite population cellulaire, enrichie après une chimiothérapie, dans la propagation d'une tumeur de cancer du poumon non à petites cellules
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 nonredundant role in tumor cell propagation in two mouse models 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 role of Notch3 in tumor propagation may provide a therapeutic target for NSCLC. "CD24, ITGB4, and Notch(1 4) enrich for TPCs in murine models of NSCLC "The TPC population is enriched after chemotherapy in the mouse model "The gene signature of mouse TPCs correlates with a poor prognosis in human NSCLC "Notch3 is required for tumor propagation in the mouse model and human NSCLC