title: Identification and Targeting of Long-Term Tumor-Propagating Cells in Small Cell Lung Cancer.
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.
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Nadine S
authors.initials: NS
authors.lastname: Jahchan
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Jing Shan
authors.initials: JS
authors.lastname: Lim
authors.affiliation: Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester and Manchester Cancer Research Centre, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: Becky
authors.initials: B
authors.lastname: Bola
authors.affiliation: Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester and Manchester Cancer Research Centre, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Morris
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Garrett
authors.initials: G
authors.lastname: Seitz
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Kim Q
authors.initials: KQ
authors.lastname: Tran
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.affiliation: Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester and Manchester Cancer Research Centre, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: Francesca
authors.initials: F
authors.lastname: Trapani
authors.affiliation: Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester and Manchester Cancer Research Centre, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Morrow
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Cristea
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Garry L
authors.initials: GL
authors.lastname: Coles
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Dian
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Dedeepya
authors.initials: D
authors.lastname: Vaka
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Kareta
authors.affiliation: 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.
authors.forename: Julie
authors.initials: J
authors.lastname: George
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Pawel K
authors.initials: PK
authors.lastname: Mazur
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Thuyen
authors.initials: T
authors.lastname: Nguyen
authors.affiliation: Stemcentrx Inc., South San Francisco, CA 94080, USA.
authors.forename: Wade C
authors.initials: WC
authors.lastname: Anderson
authors.affiliation: Stemcentrx Inc., South San Francisco, CA 94080, USA.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Dylla
authors.affiliation: Institute of Cancer Sciences, University of Manchester and Manchester Cancer Research Centre, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: Fiona
authors.initials: F
authors.lastname: Blackhall
authors.affiliation: 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.
authors.forename: Martin
authors.initials: M
authors.lastname: Peifer
authors.affiliation: Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester and Manchester Cancer Research Centre, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Dive
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: julsage@stanford.edu.
authors.forename: Julien
authors.initials: J
authors.lastname: Sage
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D051379:Mice; D055752:Small Cell Lung Carcinoma / Q000235:genetics / Q000473:pathology*; D014158:Transcription, Genetic / Q000502:physiology