Organoids of patient-derived medullary thyroid carcinoma: The first milestone towards a new in vitro model in dogs.
Dogs
Animals
Calcitonin
/ metabolism
Thyroglobulin
/ metabolism
Synaptophysin
/ metabolism
Vascular Endothelial Growth Factor A
/ metabolism
Vimentin
/ metabolism
Carboplatin
/ pharmacology
Cyclooxygenase 2
/ metabolism
Ki-67 Antigen
/ metabolism
Meloxicam
/ therapeutic use
Dog Diseases
/ pathology
Thyroid Neoplasms
/ drug therapy
Organoids
/ metabolism
ATP Binding Cassette Transporter, Subfamily B
/ metabolism
cell culture techniques
dogs
histology
immunohistochemistry
neoplasms
thyroid carcinoma
Journal
Veterinary and comparative oncology
ISSN: 1476-5829
Titre abrégé: Vet Comp Oncol
Pays: England
ID NLM: 101185242
Informations de publication
Date de publication:
Mar 2023
Mar 2023
Historique:
revised:
08
12
2022
received:
12
08
2022
accepted:
11
12
2022
pubmed:
31
12
2022
medline:
16
2
2023
entrez:
30
12
2022
Statut:
ppublish
Résumé
Organoid cultures could constitute a valuable in vitro model to explore new treatments for canine (c) medullary thyroid carcinoma (MTC). The study's objectives were to establish and characterize 3D organoid cultures of cMTC using histology and immunohistochemistry (IHC) and to evaluate the effect of antitumor drugs on organoids' viability. Five cMTC tissue samples were used to develop organoid cultures of which one organoid line, named cMTC N°2, could be passaged for an extended period. This cMTC N°2 organoid line was further compared to the primary tumour regarding morphology and IHC expression of thyroid transcription factor-1 (TTF-1), thyroglobulin, calcitonin, synaptophysin, vimentin, Ki-67, cyclooxygenase-2 (COX-2), P-glycoprotein and vascular endothelial growth factor (VEGF). Quality control of the cMTC N°2 organoid line was achieved by a single nucleotide polymorphism (SNP) array of the organoids, primary tumour and healthy blood cells of the same dog. The effect of carboplatin, meloxicam and toceranib phosphate (TOC) on cMTC N°2 organoids' viability was evaluated. The cMTC N°2 organoid line was cultured for 94 days and showed similar histological features with the primary tumour. Immunolabelling for TTF-1, thyroglobulin, calcitonin and VEGF was similar between the primary tumour and cMTC N°2 organoids. Compared to the primary tumour, organoids showed higher immunolabelling for vimentin and Ki-67, and lower immunolabelling for synaptophysin, COX-2 and P-glycoprotein. The SNP genotype was similar for each chromosome between healthy blood cells, primary tumour and cMTC N°2 organoids. Carboplatin, meloxicam and TOC had no effect on cMTC N°2 organoid cell viability within achievable in vivo concentration range. In conclusion, the cMTC N°2 organoid line is a promising first milestone towards an established in vitro organoid model to explore pathophysiology and new treatment modalities in cMTC.
Substances chimiques
Calcitonin
9007-12-9
Thyroglobulin
9010-34-8
Synaptophysin
0
Vascular Endothelial Growth Factor A
0
Vimentin
0
Carboplatin
BG3F62OND5
Cyclooxygenase 2
EC 1.14.99.1
Ki-67 Antigen
0
Meloxicam
VG2QF83CGL
ATP Binding Cassette Transporter, Subfamily B
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
111-122Subventions
Organisme : Bijzonder Onderzoeksfonds (BOF) UGent
Organisme : European Society of Veterinary Endocrinology (ESVE)
Organisme : Fonds Wetenschappelijk Onderzoek (FWO)
Informations de copyright
© 2022 John Wiley & Sons Ltd.
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