Mapping tumour heterogeneity and predictive cancer signatures in vivo
Purpose: In order to follow the fate of the bladder cells, we will use a mouse model expressing the Cre recombinase under the control of the uroplakin 2 (Upk2), a bladder specific promoter actively expressed in the bladder urothelium (Tg(Upk2-Cre)1Rkl/WghJ Jax Stock No.029281). By crossing this line with R26-Confetti (Jax Stock No.013731), the urothelial cells were specifically and irreversibly labelled with a fluorescent marker. To study the effects of immune cells, we plan to use a defective strain NSG, where immune cells are absent. This strain will allow for the bladder tumor development in the absence of inflammation and immune contributions.
Expected distress for the animals: weight loss, hematuria. Male mice develop more tumours than female mice, therefore we plan to use only NSG male mice.
Expected scientific or societal benefit: Our project aim at characterising the unknown mechanisms governing the bladder urothelial disease. We expect our research to: (1) strongly contribute to the general data base of knowledge by depositing all the omics data in public repositories following publication thus allowing further analysis and integration from other groups addressing other biological questions; (2) decisively refine the biological interpretations, by generating the spatial and temporal dynamic map of cell identity maintenance pathways dynamic in tumours and apparently normal tissue (3) uncover new strategies for tumour control by pinpointing a series of cell-plasticity targets involved in tumour initiation and progression, that can be further validated through preclinical and clinical research, hence bearing potential clinical impact in cancer treatment. (4) potentially find a common cell-plasticity switch controlling the tumour formation between different cancers. (5) understand the impact of immune response in tumor formation. This will have an obvious clinical and social impact with repercussions on the current targeted therapies.
Number of animals to be used: a total of 800 UPK2-cre; R26-Confetti transgenic mice and 90 NSG mice
Replacement, reduction and improvement
We will optimise the number of mice necessary for this project by using common experimental groups, where the same set of collected samples will be processed separately for replying distinct questions, hence reducing the number of required animals.
Expected distress for the animals: weight loss, hematuria. Male mice develop more tumours than female mice, therefore we plan to use only NSG male mice.
Expected scientific or societal benefit: Our project aim at characterising the unknown mechanisms governing the bladder urothelial disease. We expect our research to: (1) strongly contribute to the general data base of knowledge by depositing all the omics data in public repositories following publication thus allowing further analysis and integration from other groups addressing other biological questions; (2) decisively refine the biological interpretations, by generating the spatial and temporal dynamic map of cell identity maintenance pathways dynamic in tumours and apparently normal tissue (3) uncover new strategies for tumour control by pinpointing a series of cell-plasticity targets involved in tumour initiation and progression, that can be further validated through preclinical and clinical research, hence bearing potential clinical impact in cancer treatment. (4) potentially find a common cell-plasticity switch controlling the tumour formation between different cancers. (5) understand the impact of immune response in tumor formation. This will have an obvious clinical and social impact with repercussions on the current targeted therapies.
Number of animals to be used: a total of 800 UPK2-cre; R26-Confetti transgenic mice and 90 NSG mice
Replacement, reduction and improvement
We will optimise the number of mice necessary for this project by using common experimental groups, where the same set of collected samples will be processed separately for replying distinct questions, hence reducing the number of required animals.