Novel murine primary and orthotopically nasopharyngeal cancer models reveal LMP1 as a driver of metastasis

Current NPC models cannot reproduce the process of NPC tumorigenesis, which is critical for investigating the functions and mechanisms of the disease-associated factors in this malignancy.So,we aimed to generate primary and orthotopic NPC models from normal nasopharyngeal epithelium with NPC related genetic drivers. For this purpose, we cultured normal mouse nasopharyngeal organoids and induced Trp53 and Cdkn2a mutations by CRISPR/cas9 editing, together with Myc overexpression. We showed that these organoids could initiate primary NPC once transplanted into recipient mice subcutaneously or orthotopically. And we also tested the functions of LMP1 in these models and found that it dramatically promoted NPC metastases. Bulk RNA-seq of Normal nasopharyngeal organoids,Normal lung organoids; Trp53-/-;Myc;sgCdkn2a primary and metastasized tumor organoids, and Trp53-/-;Myc;sgCdkn2a; LMP1 primary and metastasized tumor organoids