Abstract
Bladder cancer is one of the most common cancers among men in industrialized countries and on the global level incidence and mortality rates are increasing. In spite of progress in surgical treatment and chemotherapy, the prognosis remains poor for patients with muscle-invasive bladder cancer. Therefore, there is a great need for the development of novel therapeutic approaches. The human amniotic membrane (hAM) is a multi-layered membrane that comprises the innermost part of the placenta. It has unique properties that make it suitable for clinical use, such as the ability to promote wound healing and decrease scarring, low immunogenicity, and immunomodulatory, antimicrobial and anticancer properties. This study aimed to investigate the effect of (i) hAM-derived cells and (ii) hAM scaffolds on the growth dynamics, proliferation rate, and invasive potential of muscle-invasive bladder cancer T24 cells. Our results show that 24 and 48 h of co-culturing T24 cells with hAM-derived cells (at 1:1 and 1:4 ratios) diminished the proliferation rate of T24 cells. Furthermore, when seeded on hAM scaffolds, namely (1) epithelium of hAM (e-hAM), (2) basal lamina of hAM (denuded; d-hAM), and (3) stroma of hAM (s-hAM), the growth dynamic of T24 cells was altered and proliferation was reduced, even more so by the e-hAM scaffolds. Importantly, despite their muscle-invasive potential, the T24 cells did not disrupt the basal lamina of hAM scaffolds. Furthermore, we observed a decrease in the expression of epithelial-mesenchymal transition (EMT) markers N-cadherin, Snail and Slug in T24 cells grown on hAM scaffolds and individual T24 cells even expressed epithelial markers E-cadherin and occludin. Our study brings new knowledge on basic mechanisms of hAM affecting bladder carcinogenesis and the results serve as a good foundation for further research into the potential of hAM-derived cells and the hAM extracellular matrix to serve as a novel bladder cancer treatment.
Highlights
549,400 people were diagnosed with bladder cancer worldwide in 2018 and as its incidence continues to increase, bladder cancer is classified among the five most common malignancies in industrialized countries (Zieger, 2008; Ferlay et al, 2015; Bray et al, 2018)
Our results show that human amniotic epithelial cells (hAEC) and human amniotic mesenchymal stromal cells (hAMSC) decrease T24 cell proliferation when cultured in direct contact with T24 cells and stronger effects were observed after 48 h of culture and at a T24:hAMSC/hAEC ratio of 1:4
HAM-Derived Cells Reduce the Proliferation of Muscle-Invasive Bladder Cancer Cells. We show that both hAMSC and hAEC reduce the proliferation of T24 cells, when cultured in direct contact with T24 cells and especially when cultured at a 1:4 T24:human amniotic membrane (hAM) cell ratio
Summary
549,400 people were diagnosed with bladder cancer worldwide in 2018 and as its incidence continues to increase, bladder cancer is classified among the five most common malignancies in industrialized countries (Zieger, 2008; Ferlay et al, 2015; Bray et al, 2018). 50–70% of patients with non-muscleinvasive bladder cancer have recurrences after surgical removal of the primary tumor, and 10–20% of those progress to muscle-invasive bladder cancer (Soloway, 2013; Yun and Kim, 2013; Ye et al, 2014; Scarpato et al, 2015; Mari et al, 2017). The development of muscle-invasive tumors (T2–T4 stage) presents a critical clinical step in carcinogenesis, which results in a significantly lower 5-year survival rate, and demands more aggressive therapy (Mari et al, 2017; Sanli et al, 2017). It is imperative to develop new therapeutic approaches that will target bladder cancer cells with high proliferative and invasive potential, which will increase the success of muscle-invasive bladder cancer treatment
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