Two cell line models to study multiorganic metastasis and immunotherapy in lung squamous cell carcinoma

Author:

Valencia Karmele1234ORCID,Sainz Cristina13,Bértolo Cristina13,de Biurrun Gabriel5,Agorreta Jackeline16,Azpilikueta Arantza7,Larrayoz Marta1258,Bosco Graziella9,Zandueta Carolina12,Redrado Miriam13,Redín Esther1238,Exposito Francisco1823ORCID,Serrano Diego183,Echepare Mirari138,Ajona Daniel1234,Melero Ignacio23910,Pio Ruben1234,Thomas Roman91112,Calvo Alfonso1238,Montuenga Luis M.1238ORCID

Affiliation:

1. Program in Solid Tumors, CIMA-University of Navarra, 31008 Pamplona, Spain

2. Consorcio de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain

3. Navarra Health Research Institute (IDISNA), 31008 Pamplona, Spain

4. Department of Biochemistry and Genetics, School of Sciences, University of Navarra, 31009 Pamplona, Spain

5. Department of Environmental Biology School of Sciences, University of Navarra, 31009 Pamplona, Spain

6. Department of Health Sciences, Biochemistry Area, Public University of Navarra, 31008 Pamplona, Spain

7. Program of Immunology and Immunotherapy, CIMA-University of Navarra, 31008 Pamplona, Spain

8. Department of Pathology, Anatomy and Physiology, School of Medicine, University of Navarra, 31009 Pamplona, Spain

9. Department of Translational Genomics, Medical Faculty, University of Cologne, 50931 Cologne, Germany

10. Department of Oncology, Clínica Universidad de Navarra, 31008 Pamplona, Spain

11. Department of Pathology, University Hospital Cologne, 50937 Cologne, Germany

12. German Cancer Research Center, German Cancer Consortium (DKTK), 69120 Heidelberg, Germany

Abstract

ABSTRACT There is a paucity of adequate mouse models and cell lines available to study lung squamous cell carcinoma (LUSC). We have generated and characterized two models of phenotypically different transplantable LUSC cell lines, i.e. UN-SCC679 and UN-SCC680, derived from A/J mice that had been chemically induced with N-nitroso-tris-chloroethylurea (NTCU). Furthermore, we genetically characterized and compared both LUSC cell lines by performing whole-exome and RNA sequencing. These experiments revealed similar genetic and transcriptomic patterns that may correspond to the classic LUSC human subtype. In addition, we compared the immune landscape generated by both tumor cells lines in vivo and assessed their response to immune checkpoint inhibition. The differences between the two cell lines are a good model for the remarkable heterogeneity of human squamous cell carcinoma. Study of the metastatic potential of these models revealed that both cell lines represent the organotropism of LUSC in humans, i.e. affinity to the brain, bones, liver and adrenal glands. In summary, we have generated valuable cell line tools for LUSC research, which recapitulates the complexity of the human disease.

Funder

Centro de Investigación Biomédica en Red de Cáncer

Fundación Científica Asociación Española Contra el Cáncer

Instituto de Salud Carlos III and ERDF

Spanish Ministry of Science and Innovation

Spanish Ministry of Education

Spanish Ministry of Health

Publisher

The Company of Biologists

Subject

General Biochemistry, Genetics and Molecular Biology,Immunology and Microbiology (miscellaneous),Medicine (miscellaneous),Neuroscience (miscellaneous)

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