Two cell line models to study multiorganic metastasis and immunotherapy in lung squamous cell carcinoma
Karmele Valencia 1 2 3 4 , Cristina Sainz 1 3 , Cristina Bértolo 1 3 , Gabriel de Biurrun 5 , Jackeline Agorreta 1 6 , Arantza Azpilikueta 7 , Marta J Larrayoz 1 8 2 3 , Graziella Bosco 9 , Carolina Zandueta 1 2 , Miriam Redrado 1 3 , Esther Redín 1 8 2 3 , Francisco Exposito 1 8 2 3 , Diego Serrano 1 8 3 , Mirari Echepare 1 8 3 , Daniel Ajona 1 2 3 4 , Ignacio Melero 2 3 7 10 , Ruben Pio 1 2 3 4 , Roman Thomas 9 11 12 , Alfonso Calvo 1 8 2 3 , Luis M Montuenga 1 8 2 3
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 (UN-SCC679 and UN-SCC680) derived from an N-nitroso-tris-chloroethylurea (NTCU) chemically-induced mouse model in A/J mice. 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 classical 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 human LUSC organotropism to the brain, bones, liver and adrenal glands.
In summary, we have generated a very valuable cell line tools for LUSC research that recapitulates the complexity of the human disease.