The Cells and Extracellular Matrix of Human Amniotic Membrane Hinder the Growth and Invasive Potential of Bladder Urothelial Cancer Cells

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. There...

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Main Authors: Taja Železnik Ramuta, Urška Dragin Jerman, Larisa Tratnjek, Aleksandar Janev, Marta Magatti, Elsa Vertua, Patrizia Bonassi Signoroni, Antonietta Rosa Silini, Ornella Parolini, Mateja Erdani Kreft
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-11-01
Series:Frontiers in Bioengineering and Biotechnology
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Online Access:https://www.frontiersin.org/articles/10.3389/fbioe.2020.554530/full
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author Taja Železnik Ramuta
Urška Dragin Jerman
Larisa Tratnjek
Aleksandar Janev
Marta Magatti
Elsa Vertua
Patrizia Bonassi Signoroni
Antonietta Rosa Silini
Ornella Parolini
Ornella Parolini
Mateja Erdani Kreft
author_facet Taja Železnik Ramuta
Urška Dragin Jerman
Larisa Tratnjek
Aleksandar Janev
Marta Magatti
Elsa Vertua
Patrizia Bonassi Signoroni
Antonietta Rosa Silini
Ornella Parolini
Ornella Parolini
Mateja Erdani Kreft
author_sort Taja Železnik Ramuta
collection DOAJ
description 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.
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spelling doaj.art-96d425e7ef104d90ac5994d4b360bf422022-12-22T00:12:21ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852020-11-01810.3389/fbioe.2020.554530554530The Cells and Extracellular Matrix of Human Amniotic Membrane Hinder the Growth and Invasive Potential of Bladder Urothelial Cancer CellsTaja Železnik Ramuta0Urška Dragin Jerman1Larisa Tratnjek2Aleksandar Janev3Marta Magatti4Elsa Vertua5Patrizia Bonassi Signoroni6Antonietta Rosa Silini7Ornella Parolini8Ornella Parolini9Mateja Erdani Kreft10Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaInstitute of Cell Biology, Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaInstitute of Cell Biology, Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaInstitute of Cell Biology, Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaCentro di Ricerca E. Menni, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, ItalyCentro di Ricerca E. Menni, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, ItalyCentro di Ricerca E. Menni, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, ItalyCentro di Ricerca E. Menni, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, ItalyDepartment of Life Science and Public Health, Università Cattolica del Sacro Cuore, Rome, ItalyFondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Rome, ItalyInstitute of Cell Biology, Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaBladder 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.https://www.frontiersin.org/articles/10.3389/fbioe.2020.554530/fullamniotic membranebladder cancertissue engineeringregenerative medicineanticanceramniotic epithelial cells
spellingShingle Taja Železnik Ramuta
Urška Dragin Jerman
Larisa Tratnjek
Aleksandar Janev
Marta Magatti
Elsa Vertua
Patrizia Bonassi Signoroni
Antonietta Rosa Silini
Ornella Parolini
Ornella Parolini
Mateja Erdani Kreft
The Cells and Extracellular Matrix of Human Amniotic Membrane Hinder the Growth and Invasive Potential of Bladder Urothelial Cancer Cells
Frontiers in Bioengineering and Biotechnology
amniotic membrane
bladder cancer
tissue engineering
regenerative medicine
anticancer
amniotic epithelial cells
title The Cells and Extracellular Matrix of Human Amniotic Membrane Hinder the Growth and Invasive Potential of Bladder Urothelial Cancer Cells
title_full The Cells and Extracellular Matrix of Human Amniotic Membrane Hinder the Growth and Invasive Potential of Bladder Urothelial Cancer Cells
title_fullStr The Cells and Extracellular Matrix of Human Amniotic Membrane Hinder the Growth and Invasive Potential of Bladder Urothelial Cancer Cells
title_full_unstemmed The Cells and Extracellular Matrix of Human Amniotic Membrane Hinder the Growth and Invasive Potential of Bladder Urothelial Cancer Cells
title_short The Cells and Extracellular Matrix of Human Amniotic Membrane Hinder the Growth and Invasive Potential of Bladder Urothelial Cancer Cells
title_sort cells and extracellular matrix of human amniotic membrane hinder the growth and invasive potential of bladder urothelial cancer cells
topic amniotic membrane
bladder cancer
tissue engineering
regenerative medicine
anticancer
amniotic epithelial cells
url https://www.frontiersin.org/articles/10.3389/fbioe.2020.554530/full
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