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

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 BlackhallMartin Peifer, Caroline Dive, Julien Sage

Research output: Contribution to journalArticle

33 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)644-656
Number of pages13
JournalCell Reports
Volume16
Issue number3
DOIs
StatePublished - Jul 19 2016

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Jahchan, N. S., Lim, J. S., Bola, B., Morris, K., Seitz, G., Tran, K. Q., Xu, L., Trapani, F., Morrow, C. J., Cristea, S., Coles, G. L., Yang, D., Vaka, D., Kareta, M. S., George, J., Mazur, P. K., Nguyen, T., Anderson, W. C., Dylla, S. J., ... Sage, J. (2016). Identification and Targeting of Long-Term Tumor-Propagating Cells in Small Cell Lung Cancer. Cell Reports, 16(3), 644-656. https://doi.org/10.1016/j.celrep.2016.06.021