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  • Selective targeting of lectins and their macropinocytosis in urothelial tumours : translation from in vitro to ex vivo
    Resnik, Nataša ...
    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.
    Source: Histochemistry and cell biology. - ISSN 0948-6143 (Vol. [ahead of print], iss. , 2023, str. 1-18)
    Type of material - article, component part
    Publish date - 2023
    Language - english
    COBISS.SI-ID - 161188867

    Link(s):

    https://link.springer.com/article/10.1007/s00418-023-02224-2
    Repository of the University of Ljubljana – RUL
    DOI

source: Histochemistry and cell biology. - ISSN 0948-6143 (Vol. [ahead of print], iss. , 2023, str. 1-18)
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