The Chick Embryo Xenograft Model for Malignant Pleural Mesothelioma: A Cost and Time Efficient 3Rs Model for Drug Target Evaluation
Malignant pleural mesothelioma (MPM) has limited treatment options and poor prognosis. Frequent inactivation of the tumour suppressors <i>BAP1</i>, <i>NF2</i> and <i>P16</i> may differentially sensitise tumours to treatments. We have established chick chorioallant...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/23/5836 |
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| author | Sarah E. Barnett Anne Herrmann Liam Shaw Elisabeth N. Gash Harish Poptani Joseph J. Sacco Judy M. Coulson |
| author_facet | Sarah E. Barnett Anne Herrmann Liam Shaw Elisabeth N. Gash Harish Poptani Joseph J. Sacco Judy M. Coulson |
| author_sort | Sarah E. Barnett |
| collection | DOAJ |
| description | Malignant pleural mesothelioma (MPM) has limited treatment options and poor prognosis. Frequent inactivation of the tumour suppressors <i>BAP1</i>, <i>NF2</i> and <i>P16</i> may differentially sensitise tumours to treatments. We have established chick chorioallantoic membrane (CAM) xenograft models of low-passage MPM cell lines and protocols for evaluating drug responses. Ten cell lines, representing the spectrum of histological subtypes and tumour suppressor status, were dual labelled for fluorescence/bioluminescence imaging and implanted on the CAM at E7. Bioluminescence was used to assess viability of primary tumours, which were excised at E14 for immunohistological staining or real-time PCR. All MPM cell lines engrafted efficiently forming vascularised nodules, however their size, morphology and interaction with chick cells varied. MPM phenotypes including local invasion, fibroblast recruitment, tumour angiogenesis and vascular remodelling were evident. Bioluminescence imaging could be used to reliably estimate tumour burden pre- and post-treatment, correlating with tumour weight and Ki-67 staining. In conclusion, MPM-CAM models recapitulate important features of the disease and are suitable to assess drug targets using a broad range of MPM cell lines that allow histological or genetic stratification. They are amenable to multi-modal imaging, potentially offering a time and cost-efficient, 3Rs-compliant alternative to rodent xenograft models to prioritise candidate compounds from in vitro studies. |
| first_indexed | 2024-03-09T17:51:59Z |
| format | Article |
| id | doaj.art-16d633c83b9d456f91783e10d4ea7dbd |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T17:51:59Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-16d633c83b9d456f91783e10d4ea7dbd2023-11-24T10:39:28ZengMDPI AGCancers2072-66942022-11-011423583610.3390/cancers14235836The Chick Embryo Xenograft Model for Malignant Pleural Mesothelioma: A Cost and Time Efficient 3Rs Model for Drug Target EvaluationSarah E. Barnett0Anne Herrmann1Liam Shaw2Elisabeth N. Gash3Harish Poptani4Joseph J. Sacco5Judy M. Coulson6Molecular Physiology & Cell Signalling, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool L69 3BX, UKMolecular Physiology & Cell Signalling, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool L69 3BX, UKMolecular Physiology & Cell Signalling, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool L69 3BX, UKMolecular and Clinical Cancer Medicine, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool L69 7ZX, UKMolecular and Clinical Cancer Medicine, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool L69 7ZX, UKMolecular and Clinical Cancer Medicine, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool L69 7ZX, UKMolecular Physiology & Cell Signalling, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool L69 3BX, UKMalignant pleural mesothelioma (MPM) has limited treatment options and poor prognosis. Frequent inactivation of the tumour suppressors <i>BAP1</i>, <i>NF2</i> and <i>P16</i> may differentially sensitise tumours to treatments. We have established chick chorioallantoic membrane (CAM) xenograft models of low-passage MPM cell lines and protocols for evaluating drug responses. Ten cell lines, representing the spectrum of histological subtypes and tumour suppressor status, were dual labelled for fluorescence/bioluminescence imaging and implanted on the CAM at E7. Bioluminescence was used to assess viability of primary tumours, which were excised at E14 for immunohistological staining or real-time PCR. All MPM cell lines engrafted efficiently forming vascularised nodules, however their size, morphology and interaction with chick cells varied. MPM phenotypes including local invasion, fibroblast recruitment, tumour angiogenesis and vascular remodelling were evident. Bioluminescence imaging could be used to reliably estimate tumour burden pre- and post-treatment, correlating with tumour weight and Ki-67 staining. In conclusion, MPM-CAM models recapitulate important features of the disease and are suitable to assess drug targets using a broad range of MPM cell lines that allow histological or genetic stratification. They are amenable to multi-modal imaging, potentially offering a time and cost-efficient, 3Rs-compliant alternative to rodent xenograft models to prioritise candidate compounds from in vitro studies.https://www.mdpi.com/2072-6694/14/23/5836mesotheliomachick embryoCAMxenograftbioluminescencefluorescence |
| spellingShingle | Sarah E. Barnett Anne Herrmann Liam Shaw Elisabeth N. Gash Harish Poptani Joseph J. Sacco Judy M. Coulson The Chick Embryo Xenograft Model for Malignant Pleural Mesothelioma: A Cost and Time Efficient 3Rs Model for Drug Target Evaluation Cancers mesothelioma chick embryo CAM xenograft bioluminescence fluorescence |
| title | The Chick Embryo Xenograft Model for Malignant Pleural Mesothelioma: A Cost and Time Efficient 3Rs Model for Drug Target Evaluation |
| title_full | The Chick Embryo Xenograft Model for Malignant Pleural Mesothelioma: A Cost and Time Efficient 3Rs Model for Drug Target Evaluation |
| title_fullStr | The Chick Embryo Xenograft Model for Malignant Pleural Mesothelioma: A Cost and Time Efficient 3Rs Model for Drug Target Evaluation |
| title_full_unstemmed | The Chick Embryo Xenograft Model for Malignant Pleural Mesothelioma: A Cost and Time Efficient 3Rs Model for Drug Target Evaluation |
| title_short | The Chick Embryo Xenograft Model for Malignant Pleural Mesothelioma: A Cost and Time Efficient 3Rs Model for Drug Target Evaluation |
| title_sort | chick embryo xenograft model for malignant pleural mesothelioma a cost and time efficient 3rs model for drug target evaluation |
| topic | mesothelioma chick embryo CAM xenograft bioluminescence fluorescence |
| url | https://www.mdpi.com/2072-6694/14/23/5836 |
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