An orthotopic model of papillary thyroid carcinoma in athymic nude mice.
OBJECTIVE
To develop a reproducible orthotopic model of papillary thyroid carcinoma for the BRAF(V600E) mutation (GenBank NM004333) and an RET/PTC rearrangement (GenBank M31213) that recapitulates the clinical picture in humans.


METHODS
In vitro and in vivo study.


METHODS
Department of Head and Neck Surgery, M. D. Anderson Cancer Center.


METHODS
Eight- to 12-week-old athymic female nude mice.


METHODS
Either BRAF-mutated or RET/PTC1-rearranged papillary thyroid carcinoma cells were injected into the thyroid glands of athymic female nude mice. The mice were euthanized when the tumor burden exceeded 1.0 cm or when they exhibited significant morbidity.


METHODS
Tumorigenicity, extent of tumor invasion and metastasis, cell invasion and migration, and median survival.


RESULTS
All the BRAF-mutated cell lines and 1 selected RET/PTC1-rearranged cell line were 100% tumorigenic in mice. These mouse tumor models exhibited a wide range of biological potential, including laryngeal invasion, lymph node metastasis, and pulmonary metastasis, thus reflecting the clinical spectrum of papillary carcinoma.


CONCLUSIONS
An orthotopic model of papillary thyroid carcinoma was successfully established in nude mice using BRAF-mutated and RET/PTC1-rearranged cell lines. These models mimic the human disease and will thus be useful for evaluating the clinical potential of novel targeted therapies.
Ahn
Soon-Hyun
SH
Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Henderson
Ying
Y
Kang
Ya'an
Y
Chattopadhyay
Chandrani
C
Holton
Paula
P
Wang
Mary
M
Briggs
Katrina
K
Clayman
Gary L
GL
D000818:Animals; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D054443:Cell Migration Assays; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D017354:Point Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology
D015514:Oncogene Proteins, Fusion; C482120:Braf protein, mouse; D048493:Proto-Oncogene Proteins B-raf