Two cell line models to study multiorganic metastasis and immunotherapy in lung squamous cell carcinoma
Keywords: 
Lung cancer
Squamous
NTCU-mouse model
Syngeneic cell lines
RNASeq
Immunotherapy
Issue Date: 
2022
ISSN: 
1754-8411
Note: 
This is an Open Access article distributed under the terms of the Creative Commons Attribution License
Citation: 
Valencia-Leoz, K. (Karmele); Sainz, C.; Bértolo-Martín de Rosales, C. (Cristina María); et al. "Two cell line models to study multiorganic metastasis and immunotherapy in lung squamous cell carcinoma". Disease model & Mechanisms. 15 (1), 2022, dmm049137
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.

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