An Orthotopic Model of Papillary Thyroid Carcinoma in Athymic Nude Mice

• Published in: Archives of otolaryngology--head & neck surgery Vol. 134; no. 2; pp. 190 - 197
• Main Authors: Ahn, Soon-Hyun, Henderson, Ying, Kang, Ya’an, Chattopadhyay, Chandrani, Holton, Paula, Wang, Mary, Briggs, Katrina, Clayman, Gary L
• Format: Journal Article
• Language: English
• Published: Chicago, IL American Medical Association 01.02.2008
• Subjects: Animals; Biological and medical sciences; Cancer; Carcinoma, Papillary - genetics; Carcinoma, Papillary - metabolism; Carcinoma, Papillary - pathology; Cell Migration Assays; Disease Models, Animal; Endocrinopathies; Female; Genetics; Immunohistochemistry; In Vitro Techniques; Malignant tumors; Medical sciences; Mice; Mice, Nude; Molecular Sequence Data; Mutation; Neoplasm Invasiveness; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Oncogene Proteins, Fusion - genetics; Otolaryngology; Otorhinolaryngology. Stomatology; Point Mutation; Proto-Oncogene Proteins B-raf - genetics; Rodents; Thyroid gland; Thyroid Neoplasms - genetics; Thyroid Neoplasms - metabolism; Thyroid Neoplasms - pathology; Thyroid. Thyroid axis (diseases); Endocrinopathy; Vertebrata; Mammalia; Mouse; Animal; Thyroid diseases; Rodentia; Models; Malignant tumor; Papillary thyroid carcinoma; Cancer
• ISSN: 0886-4470; 2168-6181; 1538-361X; 2168-619X
• DOI: 10.1001/archoto.2007.36

OBJECTIVE To develop a reproducible orthotopic model of papillary thyroid carcinoma for the BRAFV600E mutation (GenBank NM004333) and an RET/PTC rearrangement (GenBank M31213) that recapitulates the clinical picture in humans. DESIGN In vitro and in vivo study. SETTING Department of Head and Neck Surgery, M. D. Anderson Cancer Center. SUBJECTS Eight- to 12-week-old athymic female nude mice. INTERVENTIONS 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. MAIN OUTCOME MEASURES 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.Arch Otolaryngol Head Neck Surg. 2008;134(2):190-197-->