Detrimental Effect of Various Preparations of the Human Amniotic Membrane Homogenate on the 2D and 3D Bladder Cancer In vitro Models

Despite being among the ten most common cancers with high recurrence rates worldwide, there have been no major breakthroughs in the standard treatment options for bladder cancer in recent years. The use of a human amniotic membrane (hAM) to treat cancer is one of the promising ideas that have emerged in recent years. This study aimed to investigate the anticancer activity of hAM homogenate on 2D and 3D cancer models. We evaluated the effects of hAM homogenates on the human muscle invasive bladder cancer urothelial (T24) cells, papillary cancer urothelial (RT4) cells and normal porcine urothelial (NPU) cells as well as on human mammary gland non-tumorigenic (MCF10a) cells and low-metastatic breast cancer (MCF7) cells. After 24 h, we observed a gradual detachment of cancerous cells from the culture surface, while the hAM homogenate did not affect the normal cells. The most pronounced effect hAM homogenate had on bladder cancer cells; however, the potency of their detachment was dependent on the treatment protocol and the preparation of hAM homogenate. We demonstrated that hAM homogenate significantly decreased the adhesion, growth, and proliferation of human bladder invasive and papillary cancer urothelial cells and did not affect normal urothelial cells even in 7-day treatment. By using light and electron microscopy we showed that hAM homogenate disrupted the architecture of 2D and 3D bladder cancer models. The information provided by our study highlights the detrimental effect of hAM homogenate on bladder cancer cells and strengthens the idea of the potential clinical application of hAM for bladder cancer treatment.

Download Full-text

Cytotoxic and chemosensitizing effects of glycoalkaloidic extract on 2D and 3D models using RT4 and patient derived xenografts bladder cancer cells

Materials Science and Engineering C ◽

10.1016/j.msec.2020.111460 ◽

2021 ◽

Vol 119 ◽

pp. 111460

Author(s):

Mariza Abreu Miranda ◽

Priscyla Daniely Marcato ◽

Arindam Mondal ◽

Nusrat Chowdhury ◽

Aragaw Gebeyehu ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Cells ◽

3D Models ◽

Bladder Cancer Cells ◽

2D And 3D

Download Full-text

Elevated MCOLN1 Expression in p53-Deficient Bladder Cancer is Necessary for Oncogene-Induced Cell proliferation, Inflammation, and Invasion

10.1101/2020.07.08.193862 ◽

2020 ◽

Author(s):

Jewon Jung ◽

Han Liao ◽

Hong Liang ◽

John F. Hancock ◽

Catherine Denicourt ◽

...

Keyword(s):

Cell Proliferation ◽

Bladder Cancer ◽

Tumor Suppressor ◽

Cancer Cells ◽

Therapeutic Strategy ◽

Cytokine Production ◽

Urothelial Cells ◽

Tumor Suppressor P53 ◽

Wild Type ◽

Bladder Cancer Cells

SummaryInhibition of the endolysosomal cation channel, TRPML1, which is encoded by MCOLN1, deters the proliferation of cancer cells with augmented TFEB activity. Here, we report that the tumor suppressor, p53, antagonizes TFEB-driven MCOLN1 expression in bladder cancer. Not only was the constitutive loss of p53 in bladder cancer cells associated with higher MCOLN1 mRNA, knockdown of TP53 in lines with wild type alleles of the tumor suppressor increased MCOLN1 expression. Elevated TRPML1 abundance in p53-deficient cancer cells, although not sufficient for bolstering proliferation, was necessary for the effects of oncogenic HRAS on cell division, cytokine production, and invasion. These data demonstrate that hyperactivation of the TFEB– MCOLN1 transcriptional axis in urothelial cells lacking p53 permits tumorigenesis stemming from HRAS mutations. Furthermore, the insight that loss of p53 predicts addiction to TRPML1 informs an actionable therapeutic strategy for bladder cancer.

Download Full-text

FOXO1 as a tumor suppressor inactivated via AR/ERβ signals in urothelial cells

Endocrine Related Cancer ◽

10.1530/erc-20-0004 ◽

2020 ◽

Vol 27 (4) ◽

pp. 231-244 ◽

Cited By ~ 2

Author(s):

Hiroki Ide ◽

Taichi Mizushima ◽

Guiyang Jiang ◽

Takuro Goto ◽

Yujiro Nagata ◽

...

Keyword(s):

Bladder Cancer ◽

Tumor Suppressor ◽

Cancer Cells ◽

Urothelial Cancer ◽

Neoplastic Transformation ◽

Migration And Invasion ◽

Urothelial Cells ◽

Estradiol Treatment ◽

Downstream Target ◽

Bladder Cancer Cells

Androgen receptor (AR) and estrogen receptor-β (ERβ) have been implicated in urothelial tumor outgrowth as promoters, while underlying mechanisms remain poorly understood. Our transcription factor profiling previously performed identified FOXO1 as a potential downstream target of AR in bladder cancer cells. We here investigated the functional role of FOXO1 in the development and progression of urothelial cancer in relation to AR and ERβ signals. In non-neoplastic urothelial SVHUC cells or bladder cancer lines, AR/ERβ expression or dihydrotestosterone/estradiol treatment reduced the expression levels of FOXO1 gene and induced those of a phosphorylated inactive form of FOXO1 (p-FOXO1). In chemical carcinogen-induced models, FOXO1 knockdown via shRNA or inhibitor treatment resulted in considerable induction of the neoplastic transformation of urothelial cells or bladder cancer development in mice. Similarly, FOXO1 inhibition considerably induced the viability, migration, and invasion of bladder cancer cells. Importantly, in FOXO1 knockdown sublines, an anti-androgen hydroxyflutamide or an anti-estrogen tamoxifen did not significantly inhibit the neoplastic transformation of urothelial cells, while dihydrotestosterone or estradiol did not significantly promote the proliferation or migration of urothelial cancer cells. In addition, immunohistochemistry in surgical specimens showed that FOXO1 and p-FOXO1 expression was down-regulated and up-regulated, respectively, in bladder tumor tissues, which was further associated with worse patient outcomes. AR or ERβ activation is thus found to correlate with inactivation of FOXO1 which appears to be their key downstream effector. Moreover, FOXO1, as a tumor suppressor, is likely inactivated in bladder cancer, which contributes in turn to inducing urothelial carcinogenesis and cancer growth.

Download Full-text