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Article

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

by
Elisabeth Digifico
1,
Marco Erreni
2,
Federico Simone Colombo
3,
Camilla Recordati
4,
Roberta Migliore
1,
Roberta Frapolli
5,
Maurizio D’Incalci
5,
Cristina Belgiovine
1,* and
Paola Allavena
1,*
1
Laboratory of Cellular Immunology, Humanitas Clinical and Research Center - IRCCS -, Via Manzoni 56, 20089 Rozzano (MI), Italy
2
Unit of Advanced Optical Microscopy, Humanitas Clinical and Research Center - IRCCS -, Via Manzoni 56, 20089 Rozzano (MI), Italy
3
Flow Cytometry and Cell Sorting Unit, Humanitas Clinical and Research Center - IRCCS -, Via Manzoni 56, 20089 Rozzano (MI), Italy
4
Department of Veterinary Medicine, University of Milan, 26900 Lodi, Italy
5
Department of Oncology, Mario Negri Institute for Pharmacological Research - IRCCS -, 20156 Milan, Italy
*
Authors to whom correspondence should be addressed.
Cancers 2020, 12(8), 2136; https://doi.org/10.3390/cancers12082136
Submission received: 24 June 2020 / Revised: 29 July 2020 / Accepted: 30 July 2020 / Published: 1 August 2020
(This article belongs to the Section Methods and Technologies Development)
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Abstract

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.
Keywords: malignant pleural mesothelioma; MPM mouse model; in vivo imaging; intrathoracic injection; inflammation; tumor microenvironment malignant pleural mesothelioma; MPM mouse model; in vivo imaging; intrathoracic injection; inflammation; tumor microenvironment

Share and Cite

MDPI and ACS Style

Digifico, E.; Erreni, M.; Colombo, F.S.; Recordati, C.; Migliore, R.; Frapolli, R.; D’Incalci, M.; Belgiovine, C.; Allavena, P. Optimization of a Luciferase-Expressing Non-Invasive Intrapleural Model of Malignant Mesothelioma in Immunocompetent Mice. Cancers 2020, 12, 2136. https://doi.org/10.3390/cancers12082136

AMA Style

Digifico E, Erreni M, Colombo FS, Recordati C, Migliore R, Frapolli R, D’Incalci M, Belgiovine C, Allavena P. Optimization of a Luciferase-Expressing Non-Invasive Intrapleural Model of Malignant Mesothelioma in Immunocompetent Mice. Cancers. 2020; 12(8):2136. https://doi.org/10.3390/cancers12082136

Chicago/Turabian Style

Digifico, Elisabeth, Marco Erreni, Federico Simone Colombo, Camilla Recordati, Roberta Migliore, Roberta Frapolli, Maurizio D’Incalci, Cristina Belgiovine, and Paola Allavena. 2020. "Optimization of a Luciferase-Expressing Non-Invasive Intrapleural Model of Malignant Mesothelioma in Immunocompetent Mice" Cancers 12, no. 8: 2136. https://doi.org/10.3390/cancers12082136

APA Style

Digifico, E., Erreni, M., Colombo, F. S., Recordati, C., Migliore, R., Frapolli, R., D’Incalci, M., Belgiovine, C., & Allavena, P. (2020). Optimization of a Luciferase-Expressing Non-Invasive Intrapleural Model of Malignant Mesothelioma in Immunocompetent Mice. Cancers, 12(8), 2136. https://doi.org/10.3390/cancers12082136

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