A humanized stromal bed is required for engraftment of isolated human primary squamous cell carcinoma cells in immunocompromised mice

Epithelial cancers are the most common malignancies and the greatest cause of cancer mortality worldwide. The incidence of keratinocyte-derived (non-melanoma) skin cancers (NMSCa) is increasing rapidly. Despite access to abundant tumor tissue and ease of observation, acceptance of NMSCa as model carcinomas has been hindered by the lack of a reliable xenograft model. Herein we describe conditions that allow routine xenoengraftment of primary human squamous cell carcinoma (SCCa) cells. Tumor development required creation of an appropriate stromal bed prior to xenografting tumor tissue onto the backs of athymic nude mice. We also demonstrate that the stromal bed must be “humanized” if primary human SCCa is to be propagated from cell suspensions. SCCa xenografts recapitulated the histological grade and phenotype of the original tumors with considerable fidelity, even after serial passage, irrespective of the histological grade of the primary human SCCa. To our knowledge this previously unreported model can be used for drug testing, as well as for studies that are relevant to the biology of primary human SCCa and other epithelial cancers.