An immunocompetent transplantable mouse model of basal cell carcinoma

Basal cell carcinoma (BCC) is the most common type of cancer, yet mouse models of BCC are limited. Existing BCC mouse models, such as the Ptch1 ^+/--K14-CreER ^T2 p53 ^fl/fl-tumor (genetically engineered mouse BCC [GEM-BCC]) model, rely on genetic engineering. Spontaneous tumor models are essential for studying carcinogenesis; however, the heterogeneous growth of multiple tumors requires large group sizes, making them challenging to implement in early-stage drug development. This study describes the establishment of an immunocompetent transplantable BCC (Tp-BCC) mouse model suitable for preclinical treatment evaluation. By in vivo passaging of GEM-BCC tumor cells, we established a subcutaneous Tp-BCC model. We compared the microstructural features, tumor microenvironment, and transcriptional profile of the Tp-BCC model with its parental GEM-BCC model using histology, flow cytometry, and RNA sequencing. Tp-BCC tumors displayed synchronized growth and shortened time until formation compared with GEM-BCC tumors. Tp-BCC tumors showed a micro-nodular histological structure, maintained keratin 14 expression, and had a low immune infiltration similar to GEM-BCC tumors. Hedgehog signaling pathway-related genes were similarly expressed, except for Igf2. The transcriptional profile of Tp-BCC tumors was more homogeneous than that of GEM-BCC tumors. This study demonstrates that the Tp-BCC model retains key features of the GEM-BCC model and provides a complementary, immunocompetent, high-throughput platform for early-stage BCC therapeutic development.