How cancer cells attach to urinary bladder epithelium in vivo: study of the early stages of tumorigenesis in an orthotopic mouse bladder tumor model

Erman, Andreja; Kapun, Gregor; Novak, Sara; Pavlin, Mojca; Dražić, Goran; Drobne, Damjana; Veranič, Peter

doi:10.1007/s00418-018-1738-x

Cited by 8 publications

(12 citation statements)

References 33 publications

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“…It has also been used in urinary bladder pretreatment in orthotopic bladder tumor model to enhance the electrostatic interactions between tumor cells and the urothelium to increase the tumor implantation rate [21,22]. However, the results of our previous study proved that PLL (molecular weight 70–150 kDa, 0.01% concentration) caused desquamation of urothelial cells and, therefore, enabled tumor cells to attach and implant, which is in accordance with the findings of the present study [23].…”

Section: Discussionsupporting

confidence: 91%

Poly-L-lysine as an Effective and Safe Desquamation Inducer of Urinary Bladder Epithelium

2019

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Induced desquamation of urinary bladder epithelial cells, also called urothelial cells, is frequently used in studies of bladder epithelial regeneration and also in treating recurrent bacterial cystitis. Positively charged polymer chitosan is known to cause large-scale desquamation of terminally differentiated urothelial cells called umbrella cells. Aiming to compare the desquamation ability of another polycation poly-L-lysine, we studied the effect of this polymer on the functional and structural integrity of the urothelium in ex vivo and in vivo experiments. The urothelium was analyzed by measuring transepithelial electrical resistance, and the structural changes of its luminal surface were analyzed with scanning electron microscopy. The results revealed a selective and concentration-dependent desquamation effect of poly-L-lysine on superficial urothelial cells followed by quick regeneration of the urothelium, which functionally and structurally recovers in 2 to 3 h after poly-L-lysine–induced injury. Poly-L-lysine was thus proven to be a promising polymer to be used when desquamation of urothelial cells is required in basic and potentially clinical studies.

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Section: Discussionsupporting

confidence: 91%

Poly-L-lysine as an Effective and Safe Desquamation Inducer of Urinary Bladder Epithelium

2019

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“…Cancer cells used cell projections-filopodiawith expressed α3β1 integrins on their tips to adhere to less differentiated, newly exposed normal urothelial cells due to previous desquamation of superficial urothelial cells caused by PLL. Internalized metal nanoparticles served as a marker of injected cancer cells under the transmission electron microscope (TEM), while their typical rounded shape and ruffled plasma membrane were confirmed by the scanning electron microscope (SEM) as it was previously described [16] (Figure 1). Transmission electron micrograph of a CC tightly attached to the exposed basal lamina (arrows) due to previously induced urothelial cell desquamation.…”

Section: Attachment Of Urothelial Cancer Cells To Normal Urothelial Cells Is Mediated By Filopodiasupporting

confidence: 54%

“…The experimental workflow is shown in Scheme 1. First, mice were catheterized and the traumatization of the urothelium was performed by intravesical injection of poly-L-lysine (PLL) as previously described [16]. Thereafter, MB49-GFP cancer cells with internalized metal nanoparticles were inserted into the mouse bladder.…”

Section: Resultsmentioning

confidence: 99%

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How Cancer Cells Invade Bladder Epithelium and Form Tumors: The Mouse Bladder Tumor Model as a Model of Tumor Recurrence in Patients

Erman

Kamenšek

Jerman

et al. 2021

IJMS

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Non-muscle-invasive bladder cancer is the most common form of bladder cancer. The main problem in managing bladder tumors is the high recurrence after the transurethral resection of bladder tumors (TURBT). Our study aimed to examine the fate of intravesically applied cancer cells as the implantation of cancer cells after TURBT is thought to be a cause of tumor recurrence. We established an orthotopic mouse bladder tumor model with MB49-GFP cancer cells and traced them during the first three days to define their location and contacts with normal urothelial cells. Data were obtained by Western blot, immunolabeling, and light and electron microscopy. We showed that within the first two hours, applied cancer cells adhered to the traumatized epithelium by cell projections containing α3β1 integrin on their tips. Cancer cells then migrated through the epithelium and on day 3, they reached the basal lamina or even penetrated it. In established bladder tumors, E-cadherin and desmoplakin 1/2 were shown as feasible immunohistochemical markers of tumor margins based on the immunolabeling of various junctional proteins. Altogether, these results for the first time illustrate cancer cell implantation in vivo mimicking cellular events of tumor recurrence in bladder cancer patients.

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“…At adhesion to the poorly differentiated urothelial cells, both the T24 and T24 Ncad low cells formed lamellipodia and numerous filopodia. The attachment of cancer urothelial cells through the filopodia, as one of the first events of cancer urothelial cell adhesion to the urothelium, was also recently demonstrated by our research group on a model of orthotopic bladder tumor in mice [ 34 ]. We hypothesized that attachment of cancer urothelial T24 cells to the urothelium could be mediated by heterotypical E-N cadherin junctions.…”

Section: Discussionmentioning

confidence: 83%

Attachment of Cancer Urothelial Cells to the Bladder Epithelium Occurs on Uroplakin-Negative Cells and Is Mediated by Desmosomal and Not by Classical Cadherins

Jerman

Višnjar

Bratkovič

et al. 2021

IJMS

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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 Ncadlow 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 Ncadlow 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 Ncadlow cells attached to the urothelium, yet only to the uroplakin-negative urothelial cells. The ultrastructural analysis showed that T24 and T24 Ncadlow 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.

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How cancer cells attach to urinary bladder epithelium in vivo: study of the early stages of tumorigenesis in an orthotopic mouse bladder tumor model

Cited by 8 publications

References 33 publications

Poly-L-lysine as an Effective and Safe Desquamation Inducer of Urinary Bladder Epithelium

Poly-L-lysine as an Effective and Safe Desquamation Inducer of Urinary Bladder Epithelium

How Cancer Cells Invade Bladder Epithelium and Form Tumors: The Mouse Bladder Tumor Model as a Model of Tumor Recurrence in Patients

Attachment of Cancer Urothelial Cells to the Bladder Epithelium Occurs on Uroplakin-Negative Cells and Is Mediated by Desmosomal and Not by Classical Cadherins

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