Establishment of xenografts of urological cancers on chicken chorioallantoic membrane (CAM) to study metastasis.

Abstract

Cancer of the urological system commonly occurs in the kidney, bladder, and prostate gland. The clear cell subtype of renal cell carcinoma (ccRCC) constitutes the great majority of kidney cancer. Metastatic ccRCC portends a very poor outcome with no effective treatment available. Prostate cancer is the most common cancer in males in the US. Despite recent advances in selective kinase inhibitors and immunotherapies, the rate of developing new treatment from bench to bedside is slow. A time-consuming step is at the animal drug testing stage, in which the mouse model is the gold standard. In the pursuit to streamline the in vivo cancer biology research and drug development, we explored the feasibility of the chicken chorioallantoic membrane (CAM) model to establish xenografts. The CAM model greatly shortens the time of tumor growth and lowers the cost comparing to immunocompromised mice. We generated CAM xenografts from ccRCC, bladder and prostate cancer, with established cancer cell lines and freshly isolated patient-derived tissues, either as primary tumor cells or small pieces of tumors. The successful CAM engraftment rate from the different tumor sources is 70% or above. Using our previously established metastatic ccRCC mouse model, we showed that the CAM xenograft maintains the same tumor growth pattern and metastatic behavior as observed in mice. Taken together, CAM can serve as a valuable platform to establish new patient-derived xenografts (PDXs) to study tumor biology, thus accelerating the development of individualized treatment to halt the deadly metastatic stage of cancer.