Despite therapy advances, better solutions for refractory bladder cancer remain an unmet need. Human cell-based models may aid in better treatment translation. We introduce 3D-UHU-TU, a bladder cancer microtissue model which incorporates spheroids derived from low- and high-grade human bladder cancer cell lines (RT112 and T24 respectively) into a healthy human urothelium.
After model characterisation with histopathology and immunofluorescence microscopy, we trialled both the conventional chemotherapeutic Mitomycin C (MMC), and a novel herpes simplex oncolytic virus (oHSV-GFP), each assessed using confocal microscopy and cytotoxicity assays.
We observed correct expression of E- and N-Cadherin, CK7, CK20, GATA3 and Ki-67, alongside invasion and migration phenotypes. MMC treatment caused cell lysis and nuclear damage in cancer spheroids in both low- and high-grade models, with minimal damage to the surrounding healthy urothelium, and a significant increase in cleaved caspase 3 in low-grade models. oHSV-GFP co-localised in cancer spheroids and induced syncytia, spheroid disaggregation and cytotoxicity with minimal to no co-localisation or cytotoxicity in the healthy urothelium.
3D-UHU-TU model is useful for testing both treatment safety and efficacy on different grades of bladder cancer. Future use of primary tumour spheroids in place of cell lines may allow a personalised medicine approach.
British journal of cancer. 2026 Jun 02 [Epub ahead of print]
Benjamin O Murray, Jinhui Gao, Laia Pasquina-Lemonche, Katherine Swarbrick, Guy Simpson, Mark A Chambers, Hardev Pandha, Alex Freeman, Jennifer L Rohn
Centre for Kidney and Bladder Health, Division of Medicine, University College London, London, UK. ., Centre for Kidney and Bladder Health, Division of Medicine, University College London, London, UK., School of Biosciences, University of Sheffield, Sheffield, UK., Histopathology Department, Camelia Botnar Laboratories, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK., Department of Microbes, Infection and Immunity, School of Biosciences, University of Surrey, Guildford, UK., Department of Oncology, Faculty of Health and Medical Sciences, Leggett Building, University of Surrey, Guildford, Surrey, UK., Department of Pathology, University College London Hospitals NHS Foundation Trust, London, UK., Centre for Kidney and Bladder Health, Division of Medicine, University College London, London, UK. .