Journal article
Establishment of patient-derived xenografts for neuroendocrine tumors in the avian embryo model
Endocrine-related cancer, Vol.33(3), e250377
02/26/2026
DOI: 10.1530/ERC-25-0377
PMCID: PMC13034492
PMID: 41744372
Abstract
Elucidating the mechanisms underlying cancer progression and identifying tailored therapies for patients can be enhanced by using patient-derived preclinical models. In this study, we investigated whether patient-derived xenograft (PDX) models of well-differentiated neuroendocrine tumors (NETs) could be established in the avian embryo ex ovo model. We found that fresh surgical tumor samples from well-differentiated primary small-intestine and pancreatic NETs, as well as metastatic sites, exhibited engraftment rates exceeding 80% in the avian embryo model. The NET PDXs in the avian model preserved the distinct histological features of NETs, including characteristic tumor nests and the "salt and pepper" chromatin pattern in nuclei. Using immunostaining, we showed that the engrafted patient tumor fragments remained viable and maintained the proliferation rate, e.g., tumor grade, of the corresponding patient tumours. The NET PDXs continued to express characteristic neuroendocrine markers, such as the insulinoma-associated protein 1 (INSM1) transcription factor and chromogranin A (CgA). Importantly, they also retained the patient's somatostatin receptor 2 (SSTR2) expression pattern in cancer cells, which is the target of radioligand therapy. Using high-frequency ultrasound imaging and immunostaining, we also demonstrated that the engrafted tumor specimens were vascularized and exhibited functional blood perfusion. Overall, this is the first study to demonstrate the feasibility and characterize PDXs of well-differentiated NETs in the avian embryo model.
Details
- Title: Subtitle
- Establishment of patient-derived xenografts for neuroendocrine tumors in the avian embryo model
- Creators
- Nilakshi Kulathunga - Sunnybrook Health Science CentreRusha Chakraborty - Sunnybrook Health Science CentreYan Li - Sunnybrook Health Science CentreEmmanuel Cherin - Sunnybrook Health Science CentreZiyi Zoey Wang - University of TorontoSara Mar - Sunnybrook Health Science CentreTina Khazaee - Sunnybrook Health Science CentreAlexandra Misura - Sunnybrook Health Science CentreAlberto Lens-Pardo - Research Institute Hospital 12 de OctubrePo Hien Ear - University of IowaJörg Schrader - University Medical Center Hamburg-EppendorfRocio Garcia-Carbonero - Research Institute Hospital 12 de OctubreLina Chen - Sunnybrook Health Science CentreWeei-Yuarn Huang - Sunnybrook Health Science CentreHubert Tsui - Sunnybrook Health Science CentreSimron Singh - Sunnybrook Health Science CentreCalvin Law - Sunnybrook Health Science CentreJulie Hallet - Sunnybrook Health Science CentreChristine E Demore - Sunnybrook Health Science CentreHon S Leong - Sunnybrook Health Science CentreIacovos P Michael - Sunnybrook Health Science Centre
- Resource Type
- Journal article
- Publication Details
- Endocrine-related cancer, Vol.33(3), e250377
- DOI
- 10.1530/ERC-25-0377
- PMID
- 41744372
- PMCID
- PMC13034492
- NLM abbreviation
- Endocr Relat Cancer
- ISSN
- 1479-6821
- eISSN
- 1479-6821
- Publisher
- BIOSCIENTIFICA LTD
- Grant note
- Terry Fox Research Institute: 1124 Neuroendocrine Tumor Research Foundation
We sincerely thank all the patients who consented to donate samples to the Sunnybrook Biobank. We also appreciate the Sunnybrook Biobank, LMMD, and operating room staff for the initial logistical setup of the NEN Biobank, as well as NEN patient consenting. We would like to thank the contributions of the LMMD PA team (Kathryn Greenall, Tanya Jorden, Peter Leventis, Laurel Obright, Morgan Smith, Laura Stewart, Alicia Ussling) who have made the Sunnybrook Biobank and this reasearch possible. In addition, we thank the staff at Weber Farm, ON, Canada, for providing avian eggs and the Tissue Histology Core at SRI for their assistance with tissue sample preparation.
- Language
- English
- Electronic publication date
- 02/26/2026
- Academic Unit
- Surgery
- Record Identifier
- 9985139272502771
Metrics
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