Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The Chick Embryo Xenograft Model for Malignant Pleural Mesothelioma: A Cost and Time Efficient 3Rs Model for Target and Compound Evaluation

Version 1 : Received: 18 September 2022 / Approved: 20 September 2022 / Online: 20 September 2022 (02:48:17 CEST)

How to cite: Barnett, S.E.; Herrmann, A.; Gash, E.; Poptani, H.; Sacco, J.J.; Coulson, J.M. The Chick Embryo Xenograft Model for Malignant Pleural Mesothelioma: A Cost and Time Efficient 3Rs Model for Target and Compound Evaluation. Preprints 2022, 2022090285. https://doi.org/10.20944/preprints202209.0285.v1 Barnett, S.E.; Herrmann, A.; Gash, E.; Poptani, H.; Sacco, J.J.; Coulson, J.M. The Chick Embryo Xenograft Model for Malignant Pleural Mesothelioma: A Cost and Time Efficient 3Rs Model for Target and Compound Evaluation. Preprints 2022, 2022090285. https://doi.org/10.20944/preprints202209.0285.v1

Abstract

Malignant pleural mesothelioma (MPM) has limited treatment options and poor prognosis. Frequent inactivation of the tumour suppressors BAP1, NF2 and P16 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 therapies using a broad range of MPM cell lines that allow histological or genetic stratification. They are amenable to multi-modal imaging, offering a time and cost-efficient, 3Rs-compliant alternative to rodent xenograft models to prioritise candidate compounds from in vitro studies.

Keywords

mesothelioma; chick embryo; CAM; xenograft; bioluminescence; fluorescence; histology; MRI; preclinical; 3Rs

Subject

Biology and Life Sciences, Cell and Developmental Biology

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.