A surgical orthotopic approach for studying the invasive progression of human bladder cancer

• Published in: Nature protocols Vol. 14; no. 3; pp. 738 - 755
• Main Authors: Lorenzatti Hiles, Guadalupe, Cates, Angelica L., El-Sawy, Layla, Day, Kathleen C., Broses, Luke J., Han, Amy L., Briggs, Hannah L., Emamdjomeh, Amir, Chou, Andrew, Abel, Ethan V., Liebert, Monica, Palmbos, Phillip L., Udager, Aaron M., Keller, Evan T., Day, Mark L.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2019; Nature Publishing Group
• Subjects: 631/1647/767/70; 631/67/589/1336; Analytical Chemistry; Animal models; Animals; Biological Techniques; Biomedical and Life Sciences; Bladder; Bladder cancer; Cancer; Catheterization; Computational Biology/Bioinformatics; Development and progression; Diagnosis; Disease Models, Animal; Disease Progression; Humans; Implantation; Invasiveness; Laparotomy; Life Sciences; Metastases; Methods; Mice, Inbred NOD; Mice, SCID; Microarrays; Muscles; Neoplasm Invasiveness; Organic Chemistry; Protocol; Surgical equipment; Tumors; Urinary Bladder Neoplasms - pathology; Urinary Bladder Neoplasms - surgery; Urothelial cancer; Xenograft Model Antitumor Assays - methods; United States
• DOI: 10.1038/s41596-018-0112-8
• ISSN: 1754-2189; 1750-2799

The invasion of bladder cancer into the sub-urothelial muscle and vasculature are key determinants leading to lethal metastatic progression. However, the molecular basis is poorly understood, partly because of the lack of uncomplicated and reliable models that recapitulate the biology of locally invasive disease. We developed a surgical grafting technique, characterized by a simple, rapid, reproducible and high-efficiency approach, to recapitulate the pathobiological events of human bladder cancer invasion in mice. This technique consists of a small laparotomy and direct implantation of human cancer cells into the bladder lumen. Unlike other protocols, it does not require debriding of the urothelial lining, injection into the bladder wall, specialized imaging equipment, bladder catheterization or costly surgical equipment. With minimal practice, the procedure can be executed in <10 min. Tumors develop with a high take rate, and most cell lines exhibit local invasion within 4 weeks of implantation. A small laparotomy is carried out, and human cancer cells are implanted into the mouse bladder lumen. This reproduces the pathobiological events of human bladder cancer invasion in mice.