Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising/recruitment
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Recently published
    • Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Recently published
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising/recruitment
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a letter
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need Help? E-mail the JCI Insight
  • Top
  • Abstract
  • Supplemental material
  • Version history
  • Article usage
  • Citations to this article
Advertisement

Technical AdvanceIn-Press PreviewOncology Open Access | 10.1172/jci.insight.145307

Syngeneic tobacco carcinogen-induced mouse lung adenocarcinoma model exhibits PD-L1 expression and high tumor mutational burden

Laura P. Stabile,1 Vinod Kumar,2 Autumn Gaither-Davis,2 Eric H.B. Huang,2 Frank P. Vendetti,3 Princey Devadassan,2 Sanja Dacic,4 Riyue Bao,2 Richard A. Steinman,2 Timothy F. Burns,1 and Christopher J. Bakkenist3

1Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

2Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

3Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

4Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

Find articles by Stabile, L. in: JCI | PubMed | Google Scholar |

1Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

2Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

3Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

4Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

Find articles by Kumar, V. in: JCI | PubMed | Google Scholar

1Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

2Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

3Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

4Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

Find articles by Gaither-Davis, A. in: JCI | PubMed | Google Scholar

1Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

2Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

3Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

4Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

Find articles by Huang, E. in: JCI | PubMed | Google Scholar

1Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

2Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

3Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

4Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

Find articles by Vendetti, F. in: JCI | PubMed | Google Scholar

1Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

2Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

3Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

4Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

Find articles by Devadassan, P. in: JCI | PubMed | Google Scholar

1Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

2Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

3Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

4Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

Find articles by Dacic, S. in: JCI | PubMed | Google Scholar

1Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

2Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

3Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

4Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

Find articles by Bao, R. in: JCI | PubMed | Google Scholar |

1Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

2Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

3Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

4Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

Find articles by Steinman, R. in: JCI | PubMed | Google Scholar |

1Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

2Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

3Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

4Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

Find articles by Burns, T. in: JCI | PubMed | Google Scholar

1Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

2Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

3Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

4Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

Find articles by Bakkenist, C. in: JCI | PubMed | Google Scholar

Published December 22, 2020 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.145307.
Copyright © 2020, Stabile et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published December 22, 2020 - Version history
View PDF
Abstract

Human lung adenocarcinoma (LUAD) in current or former smokers exhibits a high tumor mutational burden (TMB) and distinct mutational signatures. Syngeneic mouse models of clinically relevant smoking-related LUAD are lacking. We established and characterized a tobacco-associated transplantable murine LUAD cell line, designated FVBW-17, from a LUAD induced by the tobacco carcinogen 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK) in the FVB/N mouse strain. Whole exome sequencing of FVBW-17 cells identified tobacco-associated KrasG12D and Trp53 mutations and a similar mutation profile to that of classic alkylating agents with a TMB >500. FVBW-17 cells transplanted subcutaneously, via tail vein and orthotopically generated tumors in FVB/N mice that were histologically similar to human LUAD. FVBW-17 tumors expressed PD-L1, were infiltrated with CD8+ T cells, and responsive to anti-PD-L1 therapy. FVBW-17 cells were also engineered to express green fluorescent protein and luciferase to facilitate the detection and quantification of tumor growth. Distant metastases to lung, spleen, liver, and kidney were observed from subcutaneously transplanted tumors. This novel cell line is a robust representation of human smoking-related LUAD biology and provides a much needed pre-clinical model in which to test promising new agents and combinations including immune-based therapies.

Supplemental material

View Supplemental Figure 1

Version history
  • Version 1 (December 22, 2020): In-Press Preview

Article tools

  • View PDF
  • Download citation information
  • Send a letter
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need Help? E-mail the JCI Insight

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Supplemental material
  • Version history
Advertisement
Advertisement
Follow JCI Insight:
Copyright © 2021 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts