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

Disease Models & Mechanisms

Ignacio Melero¹  Gabriel de Biurrun²  Graziella Bosco³  Roman Thomas³  Marta Larrayoz⁴  Jackeline Agorreta⁴  Mirari Echepare⁴  Daniel Ajona⁴  Francisco Exposito⁴  Cristina Sainz⁴  Diego Serrano⁴  Miriam Redrado⁴  Ruben Pio⁴  Alfonso Calvo⁴  Karmele Valencia⁴  Carolina Zandueta⁴  Luis M. Montuenga⁴  Cristina Bértolo⁴  Esther Redín⁴  Arantza Azpilikueta⁵ 

[1] Consorcio de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain;Department of Environmental Biology School of Sciences, University of Navarra, 31009 Pamplona, Spain;Department of Translational Genomics, Medical Faculty, University of Cologne, 50931 Cologne, Germany;Program in Solid Tumors, CIMA-University of Navarra, 31008 Pamplona, Spain;Program of Immunology and Immunotherapy, CIMA-University of Navarra, 31008 Pamplona, Spain;

关键词: lung cancer;    squamous;    ntcu-mouse model;    syngeneic cell lines;    rnaseq;    immunotherapy;   

DOI  :  10.1242/dmm.049137

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown