New pre-clinical model for studying human angiogenesis in Renal Cell Carcinoma

Renal cell carcinoma (RCC) accounts for 3% of adult tumors and 15,000 annual deaths in the US alone. Angiogenesis has a crucial role in RCC pathogenesis, which led to the development of anti-angiogenic drugs as a therapy for RCC. However, despite impressive results in pre-clinical models of cancer in general and RCC in particular, clinical benefit has been limited to only modest survival improvements in certain cancers, and little improvement in most RCC patients. In addition, anti-angiogenic drug response rates vary greatly between patients, and there are no markers to distinguish responders from non-responders. Therefore, observations in the current mouse models of tumor angiogenesis have limited clinical relevance for RCC. We aim to create a new pre-clinical model with both RCC and blood vessels of human origin, which we hypothesize to better mimic the disease in patients. To model tumor angiogenesis, we injected mice with human RCC cells in combination with human mesenchymal stem cells (MSCs) and endothelial colony-forming cells (ECFCs). The tumors were removed three weeks later and characterized by staining. H&E staining revealed the presence of both RCC and blood vessels. Remarkably, tumor cells and vessels formed an intertwined network, allowing them to physically and functionally interact. The human origin of these structures was confirmed by immunofluorescent staining with an HLA antibody. Overall, this model mimics the tumor-vessel interaction found in patients, enriching our understanding of human tumor-angiogenesis, and can thus serve as a personalized pre-clinical model for uncovering RCC pathogenesis and screening treatments.