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 Blackhall; Martin Peifer; Caroline Dive; Julien Sage

doi:10.1016/j.celrep.2016.06.021

Cell Reports (Jul 2016)

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 Blackhall,
Martin Peifer,
Caroline Dive,
Julien Sage

Affiliations

Nadine S. Jahchan: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA
Jing Shan Lim: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA
Becky Bola: Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester and Manchester Cancer Research Centre, Wilmslow Road, Manchester M20 4BX, UK
Karen Morris: Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester and Manchester Cancer Research Centre, Wilmslow Road, Manchester M20 4BX, UK
Garrett Seitz: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA
Kim Q. Tran: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA
Lei Xu: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA
Francesca Trapani: Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester and Manchester Cancer Research Centre, Wilmslow Road, Manchester M20 4BX, UK
Christopher J. Morrow: Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester and Manchester Cancer Research Centre, Wilmslow Road, Manchester M20 4BX, UK
Sandra Cristea: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA
Garry L. Coles: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA
Dian Yang: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA
Dedeepya Vaka: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA
Michael S. Kareta: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA
Julie George: Medical Faculty, Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn and Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany
Pawel K. Mazur: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA
Thuyen Nguyen: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA
Wade C. Anderson: Stemcentrx Inc., South San Francisco, CA 94080, USA
Scott J. Dylla: Stemcentrx Inc., South San Francisco, CA 94080, USA
Fiona Blackhall: Institute of Cancer Sciences, University of Manchester and Manchester Cancer Research Centre, Wilmslow Road, Manchester M20 4BX, UK
Martin Peifer: Medical Faculty, Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn and Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany
Caroline Dive: Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester and Manchester Cancer Research Centre, Wilmslow Road, Manchester M20 4BX, UK
Julien Sage: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA

DOI: https://doi.org/10.1016/j.celrep.2016.06.021
Journal volume & issue: Vol. 16, no. 3
pp. 644 – 656

Abstract

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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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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