Attachment of cancer urothelial cells to the bladder epithelium occurs on uroplakin-negative cells and is mediated by desmosomal and not by classical cadherins

Dragin Jerman, Urška (author), Višnjar, Tanja (author), Hafner Bratkovič, Iva (author), Resnik, Nataša (author), Pavlin, Mojca (author), Veranič, Peter (author), Erdani-Kreft, Mateja (author)

Urinary bladder cancer is often multifocal; however, the intraluminal dissemination of the urothelial cancer cells is poorly understood. The involvement of N-cadherin in the adhesion of the cancer urothelial cells to the urothelium had not previously been studied. Therefore, we herein explore the possibility of the intraluminal dissemination of the urothelial cancer cells by evaluating the role of classical cadherins in the adhesion of urothelial cancer cells to the urothelium. We used E-cadherin negative T24 cells and established a T24 Ncad$^{low}$ cell line with an additionally decreased expression of N-cadherin in the plasma membrane and a decreased secretion of proform of metalloproteinase 2. The labelled T24 and T24 Ncad$^{low}$ cells were seeded onto urothelial in vitro models. After 24 h in co-culture, unattached cancer cells were rinsed and urothelia with attached cancer urothelial cells were processed for fluorescence and electron microscopy. Both the T24 and T24 Ncad$^{low}$ cells attached to the urothelium, yet only to the uroplakin-negative urothelial cells. The ultrastructural analysis showed that T24 and T24 Ncad$^{low}$ cells adhere to poorly differentiated urothelial cells by desmosomes. To achieve this, they first disrupt tight junctions of superficial urothelial cells. This study indicates that the lack of E-cadherin expression and decreased expression of N-cadherin in the plasma membrane of T24 cells does not interfere with their adhesion to the urothelium; therefore, our results suggest that intraluminal dissemination of cancer urothelial cells along the urothelium occurs on uroplakin-negative cells and is desmosome-mediated.

• Language: English
• Keywords: bladder cancer, urothelial in vitro models, electron microscopy, N-cadherin, desmosomes
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine; FE - Faculty of Electrical Engineering
• Publication status: Published
• Publication version: Version of Record
• Year: 2021
• Number of pages: 18 str.
• Numbering: Vol. 22, iss. 11, art. 5565
• PID: 20.500.12556/RUL-135663
• UDC: 616.6
• ISSN on article: 1422-0067
• DOI: 10.3390/ijms22115565
• COBISS.SI-ID: 65359619
• Publication date in RUL: 24.03.2022

Record is a part of a journal

• Title: International journal of molecular sciences
• Shortened title: Int. j. mol. sci.
• Publisher: MDPI
• ISSN: 1422-0067
• COBISS.SI-ID: 2779162

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 01.06.2021

Secondary language

• Language: Slovenian
• Keywords: rak mehurja, urotelijski in vitro modeli, elektronska mikroskopija