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Synergic Interactions Between Hepatic Stellate Cells and Uveal Melanoma in Metastatic Growth

Uveal melanoma (UM) is a malignant intraocular tumor that spreads to the liver in half of the cases. Since hepatic cells could play a role in the therapeutic resistance of metastatic UM, the purpose of our study was to investigate the pro-invasive role of hepatic stellate cells (HSteCs) in metastati...

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Autores principales: Piquet, Léo, Dewit, Louise, Schoonjans, Nathan, Millet, Martial, Bérubé, Julie, Gerges, Peter R. A., Bordeleau, François, Landreville, Solange
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721369/
https://www.ncbi.nlm.nih.gov/pubmed/31344830
http://dx.doi.org/10.3390/cancers11081043
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author Piquet, Léo
Dewit, Louise
Schoonjans, Nathan
Millet, Martial
Bérubé, Julie
Gerges, Peter R. A.
Bordeleau, François
Landreville, Solange
author_facet Piquet, Léo
Dewit, Louise
Schoonjans, Nathan
Millet, Martial
Bérubé, Julie
Gerges, Peter R. A.
Bordeleau, François
Landreville, Solange
author_sort Piquet, Léo
collection PubMed
description Uveal melanoma (UM) is a malignant intraocular tumor that spreads to the liver in half of the cases. Since hepatic cells could play a role in the therapeutic resistance of metastatic UM, the purpose of our study was to investigate the pro-invasive role of hepatic stellate cells (HSteCs) in metastatic UM at the micro- and macro-metastatic stages. We first performed an immunostaining with the alpha-smooth muscle actin (αSMA) to localize activated HSteCs in UM liver macro-metastases from four patients. Their accumulation of collagen was assessed with Masson’s Trichrome stain. Next, we inoculated metastatic UM cells alone or with human HSteCs in triple-immunodeficient mice, in order to determine if HSteCs are recruited as early as the micro-metastatic stage. The growth of metastatic foci was imaged in the liver by ex vivo fluorescence imaging. Histological analyses were performed with Masson’s Trichrome and Picrosirius Red stains, and antibodies against Melan-A and αSMA. The collagen content was measured in xenografts by quantitative polarization microscopy. In patient hepatectomy samples, activated HSteCs and their pathological matrix were localized surrounding the malignant lesions. In the mouse xenograft model, the number of hepatic metastases was increased when human HSteCs were co-inoculated. Histological analyses revealed a significant recruitment of HSteCs near the micro/macrolesions, and an increase in fibrillar collagen production. Our results show that HSteCs can provide a permissive microenvironment and might increase the therapeutic resistance of metastatic UM.
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spelling pubmed-67213692019-09-10 Synergic Interactions Between Hepatic Stellate Cells and Uveal Melanoma in Metastatic Growth Piquet, Léo Dewit, Louise Schoonjans, Nathan Millet, Martial Bérubé, Julie Gerges, Peter R. A. Bordeleau, François Landreville, Solange Cancers (Basel) Article Uveal melanoma (UM) is a malignant intraocular tumor that spreads to the liver in half of the cases. Since hepatic cells could play a role in the therapeutic resistance of metastatic UM, the purpose of our study was to investigate the pro-invasive role of hepatic stellate cells (HSteCs) in metastatic UM at the micro- and macro-metastatic stages. We first performed an immunostaining with the alpha-smooth muscle actin (αSMA) to localize activated HSteCs in UM liver macro-metastases from four patients. Their accumulation of collagen was assessed with Masson’s Trichrome stain. Next, we inoculated metastatic UM cells alone or with human HSteCs in triple-immunodeficient mice, in order to determine if HSteCs are recruited as early as the micro-metastatic stage. The growth of metastatic foci was imaged in the liver by ex vivo fluorescence imaging. Histological analyses were performed with Masson’s Trichrome and Picrosirius Red stains, and antibodies against Melan-A and αSMA. The collagen content was measured in xenografts by quantitative polarization microscopy. In patient hepatectomy samples, activated HSteCs and their pathological matrix were localized surrounding the malignant lesions. In the mouse xenograft model, the number of hepatic metastases was increased when human HSteCs were co-inoculated. Histological analyses revealed a significant recruitment of HSteCs near the micro/macrolesions, and an increase in fibrillar collagen production. Our results show that HSteCs can provide a permissive microenvironment and might increase the therapeutic resistance of metastatic UM. MDPI 2019-07-24 /pmc/articles/PMC6721369/ /pubmed/31344830 http://dx.doi.org/10.3390/cancers11081043 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Piquet, Léo
Dewit, Louise
Schoonjans, Nathan
Millet, Martial
Bérubé, Julie
Gerges, Peter R. A.
Bordeleau, François
Landreville, Solange
Synergic Interactions Between Hepatic Stellate Cells and Uveal Melanoma in Metastatic Growth
title Synergic Interactions Between Hepatic Stellate Cells and Uveal Melanoma in Metastatic Growth
title_full Synergic Interactions Between Hepatic Stellate Cells and Uveal Melanoma in Metastatic Growth
title_fullStr Synergic Interactions Between Hepatic Stellate Cells and Uveal Melanoma in Metastatic Growth
title_full_unstemmed Synergic Interactions Between Hepatic Stellate Cells and Uveal Melanoma in Metastatic Growth
title_short Synergic Interactions Between Hepatic Stellate Cells and Uveal Melanoma in Metastatic Growth
title_sort synergic interactions between hepatic stellate cells and uveal melanoma in metastatic growth
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721369/
https://www.ncbi.nlm.nih.gov/pubmed/31344830
http://dx.doi.org/10.3390/cancers11081043
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