Identification and Targeting of Long-Term Tumor-Propagating Cells in Small Cell Lung Cancer

Publication date: Available online 30 June 2016
Source:Cell Reports
Author(s): Nadine S. Jahchan, Jing Shan Lim, Becky Bola, Karen Morris, Garrett Seitz, Kim Q. Tran, Lei Xu, Francesca Trapani, Christopher J. Morrow, Sandra Cristea, Garry L. Coles, Dian Yang, Dedeepya Vaka, Michael S. Kareta, Julie George, Pawel K. Mazur, Thuyen Nguyen, Wade C. Anderson, Scott J. Dylla, Fiona Blackhall, Martin Peifer, Caroline Dive, Julien Sage
Small cell lung cancer (SCLC) is a neuroendocrine lung cancer characterized by fast growth, early dissemination, and rapid resistance to chemotherapy. We identified a population of long-term tumor-propagating cells (TPCs) in a mouse model of SCLC. This population, marked by high levels of EpCAM and CD24, is also prevalent in human primary SCLC tumors. Murine SCLC TPCs are numerous and highly proliferative but not intrinsically chemoresistant, indicating that not all clinical features of SCLC are linked to TPCs. SCLC TPCs possess a distinct transcriptional profile compared to non-TPCs, including elevated MYC activity. Genetic and pharmacological inhibition of MYC in SCLC cells to non-TPC levels inhibits long-term propagation but not short-term growth. These studies identify a highly tumorigenic population of SCLC cells in mouse models, cell lines, and patient tumors and a means to target them in this most fatal form of lung cancer.

Graphical abstract

Teaser

Jahchan et al. use a genetically engineered mouse model of small cell lung cancer (SCLC) to functionally characterize cancer stem cells (tumor-propagating cells, TPCs). SCLC TPCs are numerous in tumors, cycle quickly, are chemosensitive, and depend on elevated MYC activity for their ability to propagate tumors.


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