دورية أكاديمية
Selective targeting of lectins and their macropinocytosis in urothelial tumours: translation from in vitro to ex vivo.
| العنوان: | Selective targeting of lectins and their macropinocytosis in urothelial tumours: translation from in vitro to ex vivo. |
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| المؤلفون: | Resnik N; Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Vrazov Trg 2, 1000, Ljubljana, Slovenia., Višnjar T; Clinical Institute of Genomic Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia., Smrkolj T; Department of Urology, University Medical Centre Ljubljana, Ljubljana, Slovenia.; Department of Surgery, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia., Kreft ME; Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Vrazov Trg 2, 1000, Ljubljana, Slovenia., Romih R; Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Vrazov Trg 2, 1000, Ljubljana, Slovenia., Zupančič D; Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Vrazov Trg 2, 1000, Ljubljana, Slovenia. dasa.zupancic@mf.uni-lj.si. |
| المصدر: | Histochemistry and cell biology [Histochem Cell Biol] 2023 Nov; Vol. 160 (5), pp. 435-452. Date of Electronic Publication: 2023 Aug 03. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Springer Country of Publication: Germany NLM ID: 9506663 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-119X (Electronic) Linking ISSN: 09486143 NLM ISO Abbreviation: Histochem Cell Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Berlin : Springer, |
| مواضيع طبية MeSH: | Lectins*/metabolism , Urinary Bladder Neoplasms*/pathology, Humans ; Endocytosis/physiology ; Urinary Bladder/metabolism ; Endosomes/metabolism ; Plant Lectins/pharmacology ; Plant Lectins/metabolism ; Plant Lectins/therapeutic use |
| مستخلص: | 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. (© 2023. The Author(s).) |
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| فهرسة مساهمة: | Keywords: Cancer urothelial cells; Endocytosis; Glycosylation; Lectins; Macropinocytosis; Urinary bladder tumours |
| المشرفين على المادة: | 0 (Lectins) 0 (Plant Lectins) |
| تواريخ الأحداث: | Date Created: 20230803 Date Completed: 20231106 Latest Revision: 20231106 |
| رمز التحديث: | 20231106 |
| مُعرف محوري في PubMed: | PMC10624759 |
| DOI: | 10.1007/s00418-023-02224-2 |
| PMID: | 37535087 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1432-119X |
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| DOI: | 10.1007/s00418-023-02224-2 |