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

Journal: 
Cell Rep
Publication Year: 
2016
Authors: 
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
PubMed link: 
27373157
Public Summary: 
Small cell lung cancer (SCLC) is a neuroendocrine subtype of 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 p roliferative but not intrinsically chemoresistant, indicating that not all the 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 longterm 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.
Scientific Abstract: 
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.