Selective targeting of lectins and their macropinocytosis in urothelial tumours

translation from in vitro to ex vivo

Nataša Resnik (Author), Tanja Višnjar (Author), Tomaž Smrkolj (Author), Mateja Erdani-Kreft (Author), Rok Romih (Author), Daša Zupančič (Author)

Abstract

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.

Keywords

cancer urothelial cells;endocytosis;glycosylation;lectins;endometriosis;non-invasive diagnosis;macropinocytosis;urinary bladder tumours;

Data

Language:	English
Year of publishing:	2023
Typology:	1.01 - Original Scientific Article
Organization:	UL MF - Faculty of Medicine
UDC:	616-006:576
COBISS:	161188867
ISSN:	0948-6143
Views:	988
Downloads:	39
Average score:	0 (0 votes)
Metadata:

Other data

Secondary language:	Slovenian
Secondary keywords:	urotelijske celice raka;endocitoza;glikozilacija;lektini;makropinocitoza;tumorji sečnega mehurja;
Type (COBISS):	Article
Pages:	str. 435-452
Volume:	ǂVol. ǂ [ahead of print]
Issue:	ǂVol. ǂ 160
Chronology:	2023
DOI:	10.1007/s00418-023-02224-2
ID:	21281436