[PDF][PDF] A rare population of CD24+ ITGB4+ Notchhi cells drives tumor propagation in NSCLC and requires Notch3 for self-renewal

Y Zheng, CC de la Cruz, LC Sayles, C Alleyne-Chin… - Cancer cell, 2013 - cell.com
Y Zheng, CC de la Cruz, LC Sayles, C Alleyne-Chin, D Vaka, TD Knaak, M Bigos, Y Xu
Cancer cell, 2013cell.com
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+ Notch hi 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 …
Summary
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.
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