Selective targeting of lectins and their macropinocytosis in urothelial tumours

translation from in vitro to ex vivo

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

Povzetek

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.

Ključne besede

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

Podatki

Jezik:	Angleški jezik
Leto izida:	2023
Tipologija:	1.01 - Izvirni znanstveni članek
Organizacija:	UL MF - Medicinska fakulteta
UDK:	616-006:576
COBISS:	161188867
ISSN:	0948-6143
Št. ogledov:	988
Št. prenosov:	39
Ocena:	0 (0 glasov)
Metapodatki:

Ostali podatki

Sekundarni jezik:	Slovenski jezik
Sekundarne ključne besede:	urotelijske celice raka;endocitoza;glikozilacija;lektini;makropinocitoza;tumorji sečnega mehurja;
Vrsta dela (COBISS):	Članek v reviji
Strani:	str. 435-452
Letnik:	ǂVol. ǂ [ahead of print]
Zvezek:	ǂVol. ǂ 160
Čas izdaje:	2023
DOI:	10.1007/s00418-023-02224-2
ID:	21281436