20.500.12556/RUL-152547 Selective targeting of lectins and their macropinocytosis in urothelial tumours translation from in vitro to ex vivo Urinary bladder cancer can be treated by intravesical application of therapeutic agents, but the specific targeting of cancer urothelial cells and the endocytotic pathways of the agents are not known. During carcinogenesis, the superficial urothelial cells exhibit changes in sugar residues on the apical plasma membranes. This can be exploited for selective targeting from the luminal side of the bladder. Here we show that the plant lectins Jacalin (from Artocarpus integrifolia), ACA (from Amaranthus caudatus) and DSA (from Datura stramonium) selectively bind to the apical plasma membrane of low- (RT4) and high-grade (T24) cancer urothelial cells in vitro and urothelial tumours ex vivo. The amount of lectin binding was significantly different between RT4 and T24 cells. Endocytosis of lectins was observed only in cancer urothelial cells and not in normal urothelial cells. Transmission electron microscopy analysis showed macropinosomes, endosome-like vesicles and multivesicular bodies filled with lectins in RT4 and T24 cells and also in cells of urothelial tumours ex vivo. Endocytosis of Jacalin and ACA in cancer cells was decreased in vitro after addition of inhibitor of macropinocytosis 5-(N-ethyl-N-isopropyl) amiloride (EIPA) and increased after stimulation of macropinocytosis with epidermal growth factor (EGF). Clathrin, caveolin and flotillin did not colocalise with lectins. These results confirm that the predominant mechanism of lectin endocytosis in cancer urothelial cells is macropinocytosis. Therefore, we propose that lectins in combination with conjugated therapeutic agents are promising tools for improved intravesical therapy by targeting cancer cells. cancer urothelial cells endocytosis glycosylation lectins endometriosis non-invasive diagnosis macropinocytosis urinary bladder tumours urotelijske celice raka endocitoza glikozilacija lektini makropinocitoza tumorji sečnega mehurja true false true Angleški jezik Slovenski jezik Članek v reviji 2023-11-27 12:27:57 2023-11-27 12:28:01 2024-09-30 11:28:45 0000-00-00 00:00:00 2023 0 0 Str. 435–452 iss. 5 Vol. 160 2023 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616-006:576 0948-6143 10.1007/s00418-023-02224-2 161188867 s00418-023-02224-2.pdf s00418-023-02224-2.pdf 1 1B952D3B1AAA071AC819559BF80ADE0D 01476196b46371ce3b9afdb32c336c022f44b2c08389379227005bec853cfe6d 493259fe-8d18-11ee-8ac8-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=178077 https://link.springer.com/article/10.1007/s00418-023-02224-2 1 06ff6e7b-8d18-11ee-8ac8-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=178076 Medicinska fakulteta 0 0 0