title: Selective binding of lectins to normal and neoplastic urothelium in rat and mouse bladder carcinogenesis models.
abstract: Bladder cancer adjuvant intravesical therapy could be optimized by more selective targeting of neoplastic tissue via specific binding of lectins to plasma membrane carbohydrates. Our aim was to establish rat and mouse models of bladder carcinogenesis to investigate in vivo and ex vivo binding of selected lectins to the luminal surface of normal and neoplastic urothelium. Male rats and mice were treated with 0.05 % N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in drinking water and used for ex vivo and in vivo lectin binding experiments. Urinary bladder samples were also used for paraffin embedding, scanning electron microscopy and immunofluorescence labelling of uroplakins. During carcinogenesis, the structure of the urinary bladder luminal surface changed from microridges to microvilli and ropy ridges and the expression of urothelial-specific glycoproteins uroplakins was decreased. Ex vivo and in vivo lectin binding experiments gave comparable results. Jacalin (lectin from Artocarpus integrifolia) exhibited the highest selectivity for neoplastic compared to normal urothelium of rats and mice. The binding of lectin from Amaranthus caudatus decreased in rat model and increased in mouse carcinogenesis model, indicating interspecies variations of plasma membrane glycosylation. Lectin from Datura stramonium showed higher affinity for neoplastic urothelium compared to the normal in rat and mouse model. The BBN-induced animal models of bladder carcinogenesis offer a promising approach for lectin binding experiments and further lectin-mediated targeted drug delivery research. Moreover, in vivo lectin binding experiments are comparable to ex vivo experiments, which should be considered when planning and optimizing future research.
authors.affiliation: Faculty of Medicine, Institute of Cell Biology, Vrazov trg 2, 1000, Ljubljana, Slovenia, dasa.zupancic@mf.uni-lj.si.
authors.forename: Daša
authors.initials: D
authors.lastname: Zupančič
authors.forename: Mateja Erdani
authors.initials: ME
authors.lastname: Kreft
authors.forename: Rok
authors.initials: R
authors.lastname: Romih
mesh_terms: D000818:Animals; D001665:Binding Sites; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D037102:Lectins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008855:Microscopy, Electron, Scanning; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology*; D019459:Urothelium / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D037102:Lectins