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-CreERT2p53fl/fl-tumor (GEM-BCC) model rely on genetic engineering. These models are essential for studying BCC carcinogenesis but are complicated to integrate into preclinical treatment evaluation studies due to the spontaneous growth of multiple tumors with heterogenous growth. This study describes the establishment of an immunocompetent transplantable BCC (Tp-BCC) mouse model suitable for preclinical treatment evaluation. By in vivo passaging GEM-BCC tumor cells, we were able to establish a Tp-BCC model. We compared 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 tumor formation compared to GEM-BCC tumors. Tp-BCC tumors showed micro-nodular histological structure and had a tumor immune microenvironment composition similar to the GEM-BCC tumors. Hedgehog signaling pathway-related genes were similarly expressed except for Igf2. The transcriptional profile of Tp-BCC model was less variable than the GEM-BCC model. This study demonstrates that the Tp-BCC model resembles the clinically relevant GEM-BCC model while providing an immunocompetent high-throughput model for evaluating treatments of BCC.