High-grade urothelial cell carcinoma of the bladder has a poor prognosis when
lymph nodes are involved. Despite curative therapy for clinically-localized disease,
over half of the muscle-invasive urothelial cell carcinoma patients will develop
metastases and die within 5 years. There are currently no described xenograft
models that consistently mimic urothelial cell carcinoma metastasis. To develop a
patient-derived orthotopic xenograft model to mimic clinical urothelial cell carcinoma
progression to metastatic disease, the urothelial cell carcinoma cell line UM-UC-3 and
two urothelial cell carcinoma patient specimens were doubly tagged with Luciferase/
RFP and were intra-vesically (IB) instilled into N... More
High-grade urothelial cell carcinoma of the bladder has a poor prognosis when
lymph nodes are involved. Despite curative therapy for clinically-localized disease,
over half of the muscle-invasive urothelial cell carcinoma patients will develop
metastases and die within 5 years. There are currently no described xenograft
models that consistently mimic urothelial cell carcinoma metastasis. To develop a
patient-derived orthotopic xenograft model to mimic clinical urothelial cell carcinoma
progression to metastatic disease, the urothelial cell carcinoma cell line UM-UC-3 and
two urothelial cell carcinoma patient specimens were doubly tagged with Luciferase/
RFP and were intra-vesically (IB) instilled into NOD/SCID mice with or without lymph
node stromal cells (HK cells). Mice were monitored weekly with bioluminescence
imaging to assess tumor growth and metastasis. Primary tumors and organs were
harvested for bioluminescence imaging, weight, and formalin-fixed for hematoxylin
and eosin and immunohistochemistry staining. In this patient-derived orthotopic
xenograft model, xenograft tumors showed better implantation rates than currently
reported using other models. Xenograft tumors histologically resembled pre-implanted
primary specimens from patients, presenting muscle-invasive growth patterns. In
the presence of HK cells, tumor formation, tumor angiogenesis, and distant organ
metastasis were significantly enhanced in both UM-UC-3 cells and patient-derived
specimens. Thus, we established a unique, reproducible patient-derived orthotopic
xenograft model using human high-grade urothelial cell carcinoma cells and lymph
node stromal cells. It allows for investigating the mechanism involved in tumor
formation and metastasis, and therefore it is useful for future testing the optimal
sequence of conventional drugs or the efficacy of novel therapeutic drugs.