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Optimization of a Luciferase-Expressing Non-Invasive Intrapleural Model of Malignant Mesothelioma in Immunocompetent Mice

Malignant Pleural Mesothelioma (MPM) is an aggressive tumor of the pleural lining that is usually identified at advanced stages and resistant to current therapies. Appropriate pre-clinical mouse tumor models are of pivotal importance to study its biology. Usually, tumor cells have been injected intr...

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Autores principales: Digifico, Elisabeth, Erreni, Marco, Colombo, Federico Simone, Recordati, Camilla, Migliore, Roberta, Frapolli, Roberta, D’Incalci, Maurizio, Belgiovine, Cristina, Allavena, Paola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465989/
https://www.ncbi.nlm.nih.gov/pubmed/32752156
http://dx.doi.org/10.3390/cancers12082136
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author Digifico, Elisabeth
Erreni, Marco
Colombo, Federico Simone
Recordati, Camilla
Migliore, Roberta
Frapolli, Roberta
D’Incalci, Maurizio
Belgiovine, Cristina
Allavena, Paola
author_facet Digifico, Elisabeth
Erreni, Marco
Colombo, Federico Simone
Recordati, Camilla
Migliore, Roberta
Frapolli, Roberta
D’Incalci, Maurizio
Belgiovine, Cristina
Allavena, Paola
author_sort Digifico, Elisabeth
collection PubMed
description Malignant Pleural Mesothelioma (MPM) is an aggressive tumor of the pleural lining that is usually identified at advanced stages and resistant to current therapies. Appropriate pre-clinical mouse tumor models are of pivotal importance to study its biology. Usually, tumor cells have been injected intraperitoneally or subcutaneously. Using three available murine mesothelioma cell lines with different histotypes (sarcomatoid, biphasic, epithelioid), we have set up a simplified model of in vivo growth orthotopically by inoculating tumor cells directly in the thorax with a minimally invasive procedure. Mesothelioma tumors grew along the pleura and spread on the superficial areas of the lungs, but no masses were found outside the thoracic cavity. As observed in human MPM, tumors were highly infiltrated by macrophages and T cells. The luciferase-expressing cells can be visualized in vivo by bioluminescent optical imaging to precisely quantify tumor growth over time. Notably, the bioluminescence signal detected in vivo correctly matched the tumor burden quantified with classical histology. In contrast, the subcutaneous or intraperitoneal growth of these mesothelioma cells was considered either non-representative of the human disease or unreliable to precisely quantify tumor load. Our non-invasive in vivo model of mesothelioma is simple and reproducible, and it reliably recapitulates the human disease.
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spelling pubmed-74659892020-09-14 Optimization of a Luciferase-Expressing Non-Invasive Intrapleural Model of Malignant Mesothelioma in Immunocompetent Mice Digifico, Elisabeth Erreni, Marco Colombo, Federico Simone Recordati, Camilla Migliore, Roberta Frapolli, Roberta D’Incalci, Maurizio Belgiovine, Cristina Allavena, Paola Cancers (Basel) Article Malignant Pleural Mesothelioma (MPM) is an aggressive tumor of the pleural lining that is usually identified at advanced stages and resistant to current therapies. Appropriate pre-clinical mouse tumor models are of pivotal importance to study its biology. Usually, tumor cells have been injected intraperitoneally or subcutaneously. Using three available murine mesothelioma cell lines with different histotypes (sarcomatoid, biphasic, epithelioid), we have set up a simplified model of in vivo growth orthotopically by inoculating tumor cells directly in the thorax with a minimally invasive procedure. Mesothelioma tumors grew along the pleura and spread on the superficial areas of the lungs, but no masses were found outside the thoracic cavity. As observed in human MPM, tumors were highly infiltrated by macrophages and T cells. The luciferase-expressing cells can be visualized in vivo by bioluminescent optical imaging to precisely quantify tumor growth over time. Notably, the bioluminescence signal detected in vivo correctly matched the tumor burden quantified with classical histology. In contrast, the subcutaneous or intraperitoneal growth of these mesothelioma cells was considered either non-representative of the human disease or unreliable to precisely quantify tumor load. Our non-invasive in vivo model of mesothelioma is simple and reproducible, and it reliably recapitulates the human disease. MDPI 2020-08-01 /pmc/articles/PMC7465989/ /pubmed/32752156 http://dx.doi.org/10.3390/cancers12082136 Text en © 2020 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
Digifico, Elisabeth
Erreni, Marco
Colombo, Federico Simone
Recordati, Camilla
Migliore, Roberta
Frapolli, Roberta
D’Incalci, Maurizio
Belgiovine, Cristina
Allavena, Paola
Optimization of a Luciferase-Expressing Non-Invasive Intrapleural Model of Malignant Mesothelioma in Immunocompetent Mice
title Optimization of a Luciferase-Expressing Non-Invasive Intrapleural Model of Malignant Mesothelioma in Immunocompetent Mice
title_full Optimization of a Luciferase-Expressing Non-Invasive Intrapleural Model of Malignant Mesothelioma in Immunocompetent Mice
title_fullStr Optimization of a Luciferase-Expressing Non-Invasive Intrapleural Model of Malignant Mesothelioma in Immunocompetent Mice
title_full_unstemmed Optimization of a Luciferase-Expressing Non-Invasive Intrapleural Model of Malignant Mesothelioma in Immunocompetent Mice
title_short Optimization of a Luciferase-Expressing Non-Invasive Intrapleural Model of Malignant Mesothelioma in Immunocompetent Mice
title_sort optimization of a luciferase-expressing non-invasive intrapleural model of malignant mesothelioma in immunocompetent mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465989/
https://www.ncbi.nlm.nih.gov/pubmed/32752156
http://dx.doi.org/10.3390/cancers12082136
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