Open AccessTwo cell line models to study multiorganic metastasis and immunotherapy in lung squamous cell carcinoma
Author(s) -
Karmele Valencia,
Cristina Sainz,
Cristina Bértolo,
Gabriel de Biurrun,
Jackeline Agorreta,
Arantza Azpilikueta,
Marta Larráyoz,
Graziella Bosco,
Carolina Zandueta,
Miriam Redrado,
Esther Redín,
Francisco J. Expósito,
Diego Serrano,
Álvaro Teijeira,
Daniel Ajona,
Ignacio Melero,
Rubén Pı́o,
Roman K. Thomas,
Alfonso Calvo,
Luis M. Montuenga
Publication year - 2022
Publication title -
disease models and mechanisms
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.327
H-Index - 83
eISSN - 1754-8411
pISSN - 1754-8403
DOI - 10.1242/dmm.049137
Subject(s) - cell culture , biology , cancer research , cell , immunotherapy , metastasis , immune system , immunology , cancer , genetics
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.